Direct association of Mu-Opioid and NMDA glutamate receptors supports their cross-regulation: Molecular implications for opioid tolerance

Current Drug Abuse Reviews

Volumn 5, Issue 3, 2012, Pages 199-226

  Garzón, Javier ^a   Rodríguez Muñoz, María ^a   Sánchez Blázquez, Pilar ^a  

^a INSTITUTO CAJAL   (Spain)

Author keywords

Analgesia; Antinociception; Calciumcalmodulin dependent kinase II; Morphine; Mu opioid receptor; Nervous tissue; Nitric oxide synthase; NMDA receptor; Opioid; Protein kinase A; Protein kinase C; Receptor desensitization; Receptor tolerance; Redox signaling; Regulators of G protein signaling proteins; Zinc ions

Indexed keywords

AGMATINE; BROMOCRIPTINE; CALCITONIN GENE RELATED PEPTIDE; CALCIUM; CALMODULIN; CHOLECYSTOKININ; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIN DEPENDENT KINASE 2; CYCLOOXYGENASE 2 INHIBITOR; DELTA OPIATE RECEPTOR; G PROTEIN COUPLED RECEPTOR; GLUTAMATE RECEPTOR; GLUTAMIC ACID; GLUTAMINE; MORPHINE; MU OPIATE RECEPTOR; N METHYL DEXTRO ASPARTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NIFEDIPINE; NIMESULIDE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NOLPITANTIUM; OPIATE; OXYTOCIN; PROTEIN KINASE C; RITANSERIN; SUBSTANCE P; UNINDEXED DRUG; VERAPAMIL;

ARTICLE; BRAIN CORTEX; BRAIN STEM; CEREBELLUM; CORPUS STRIATUM; DESENSITIZATION; DRUG ABUSE; DRUG MECHANISM; DRUG TOLERANCE; HIPPOCAMPUS; HUMAN; IMMUNOREACTIVITY; MOUSE; NERVOUS SYSTEM; NONHUMAN; PRIORITY JOURNAL; RAT; THALAMUS;

ANALGESICS, OPIOID; ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG TOLERANCE; HUMANS; MODELS, BIOLOGICAL; MORPHINE; OPIOID-RELATED DISORDERS; RECEPTOR CROSS-TALK; RECEPTORS, N-METHYL-D-ASPARTATE; RECEPTORS, OPIOID, MU; SIGNAL TRANSDUCTION;

EID: 84869138744     PISSN: 18744737     EISSN: 18744745     Source Type: Journal    
DOI: 10.2174/1874473711205030199     Document Type: Article

References (304)

1. Huidobro F, Huidobro-Toro JP, Way EL. Studies on tolerance development to single doses of morphine in mice. J Pharmacol Exp Ther 1976; 198: 318-29.
2. Kornetsky C, Bain G. Morphine: single-dose tolerance. Science 1968; 162: 1011-2.
3. Fairbanks CA, Wilcox GL. Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance. J Pharmacol Exp Ther 1997; 282: 1408-17.
4. Bilsky EJ, Bernstein RN, Wang Z, Sadee W, Porreca F. Effects of naloxone and D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 and the protein kinase inhibitors H7 and H8 on acute morphine dependence and antinociceptive tolerance in mice. J Pharmacol Exp Ther 1996; 277: 484-90.
5. Huidobro-Toro JP, Way EL. Single-dose tolerance to antinociception, and physical dependence on beta-endorphin in mice. Eur J Pharmacol 1978; 52: 179-89.
6. Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P, Garzón J. Morphine induces endocytosis of neuronal m-opioid receptors through the sustained transfer of Ga subunits to RGSZ2 proteins. Mol Pain 2007; 3: 19.
7. Rodríguez-Muñoz M, Sánchez-Blázquez P, Vicente-Sánchez A, Berrocoso E, Garzón J. The Mu-Opioid Receptor and the NMDA Receptor Associate in PAG Neurons: Implications in Pain Control. Neuropsychopharmacology 2012; 37: 338-49.
8. He L, Fong J, von Zastrow M, Whistler JL. Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell 2002; 108: 271-82.
9. Marie N, Aguila B, Allouche S. Tracking the opioid receptors on the way of desensitization. Cell Signal 2006; 18: 1815-33.
10. Wang ZJ, Wang LX. Phosphorylation: a molecular switch in opioid tolerance. Life Sci 2006; 79: 1681-91.
11. Finn AK, Whistler JL. Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal. Neuron 2001; 32: 829-39.
12. Tsao P, von Zastrow M. Downregulation of G protein-coupled receptors. Curr Opin Neurobiol 2000; 10: 365-9.
13. Quillinan N, Lau EK, Virk M, von ZM, Williams JT. Recovery from mu-opioid receptor desensitization after chronic treatment with morphine and methadone. J Neurosci 2011; 31: 4434-43.
14. Dang VC, Chieng B, Azriel Y, Christie MJ. Cellular morphine tolerance produced by barrestin-2-dependent impairment of muopioid receptor resensitization. J Neurosci 2011; 31: 7122-30.
15. oa subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice. Neuropharmacology 1999; 38: 1861-73.
16. i2a subunits prevents acute tolerance (tachyphylaxis) to mu-opioid effects in mice. Neuropharmacology 2001; 40: 560-9.
17. Maher CE, Martin TJ, Childers SR. Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration. Life Sci 2005; 77: 1140-54.
18. Sim-Selley LJ, Selley DE, Vogt LJ, Childers SR, Martin TJ. Chronic heroin self-administration desensitizes m opioid receptoractivated G-proteins in specific regions of rat brain. J Neurosci 2000; 20: 4555-62.
19. 35S]GTPgS autoradiography in rat brain. J Neurosci 1996; 16: 2684-92.
20. Garzón J, Rodríguez-Díaz M, López-Fando A, Sánchez-Blázquez P. RGS9 proteins facilitate acute tolerance to mu-opioid effects. Eur J Neurosci 2001; 13: 801-11.
21. Garzón J, Rodríguez-Díaz M, López-Fando A, García-España A, Sánchez-Blázquez P. Glycosylated phosducin-like protein long regulates opioid receptor function in mouse brain. Neuropharmacology 2002; 42: 813-28.
22. Garzón J, Rodriguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P. Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS. Psychopharmacology (Berl) 2005; 180: 1-11.
23. Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, Garzón J. RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Gaz subunits. Neuropharmacology 2005; 48: 134-50.
24. Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P. Activation of m-opioid receptors transfers control of Ga subunits to the regulator of G-protein signaling RGS9-2: role in receptor desensitization. J Biol Chem 2005; 280: 8951-60.
25. Psifogeorgou K, Terzi D, Papachatzaki MM, et al. A unique role of RGS9-2 in the striatum as a positive or negative regulator of opiate analgesia. J Neurosci 2011; 31: 5617-24.
26. Ibi M, Matsuno K, Matsumoto M, et al. Involvement of NOX1/NADPH Oxidase in Morphine-Induced Analgesia and Tolerance. J Neurosci 2011; 31: 18094-103.
27. Zarrindast MR, Nikfar S, Rezayat M. Cholecystokinin receptor mechanism(s) and morphine tolerance in mice. Pharmacol Toxicol 1999; 84: 46-50.
28. Rezayat M, Nikfar S, Zarrindast MR. CCK receptor activation may prevent tolerance to morphine in mice. Eur J Pharmacol 1994; 254: 21-6.
29. van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 1997; 21: 649-78.
30. Kangrga I, Randic M. Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice. J Neurosci 1990; 10: 2026-38.
31. Menard DP, van RD, Kar S, et al. A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia. J Neurosci 1996; 16: 2342-51.
32. Wang D, Chen P, Li Q, Quirion R, Hong Y. Blockade of adrenomedullin receptors reverses morphine tolerance and its neurochemical mechanisms. Behav Brain Res 2011; 221: 83-90.
33. Powell KJ, Ma W, Sutak M, et al. Blockade and reversal of spinal morphine tolerance by peptide and non-peptide calcitonin generelated peptide receptor antagonists. Br J Pharmacol 2000; 131: 875-84.
34. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999; 51: 7-61.
35. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 2006; 5: 160-70.
36. Maeng S, Zarate Jr CA. The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep 2007; 9: 467-74.
37. Mechri A, Saoud M, Khiari G, et al. Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine. Encephale 2001; 27: 53-9.
38. Chapman V, Haley JE, Dickenson AH. Electrophysiologic analysis of preemptive effects of spinal opioids on N-methyl-D-aspartate receptor-mediated events. Anesthesiology 1994; 81: 1429-35.
39. Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain 2009; 145: 304-11.
40. Mori H, Mishina M. Structure and function of the NMDA receptor channel. Neuropharmacology 1995; 34: 1219-37.
41. Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci U S A 1991; 88: 6368-71.
42. Fedele E, Raiteri M. In vivo studies of the cerebral glutamate receptor/NO/cGMP pathway. Prog Neurobiol 1999; 58: 89-120.
43. Inoue M, Mishina M, Ueda H. Locus-specific rescue of GluRe1 NMDA receptors in mutant mice identifies the brain regions important for morphine tolerance and dependence. J Neurosci 2003; 23: 6529-36.
44. Pasternak GW, Kolesnikov YA, Babey AM. Perspectives on the Nmethyl-D-aspartate/nitric oxide cascade and opioid tolerance. Neuropsychopharmacology 1995; 13: 309-13.
45. Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 1991; 251: 85-7.
46. Trujillo KA. The neurobiology of opiate tolerance, dependence and sensitization: mechanisms of NMDA receptor-dependent synaptic plasticity. Neurotox Res 2002; 4: 373-91.
47. Narita M, Hashimoto K, Amano T, et al. Post-synaptic action of morphine on glutamatergic neuronal transmission related to the descending antinociceptive pathway in the rat thalamus. J Neurochem 2008; 104: 469-78.
48. Koyama S, Akaike N. Activation of mu-opioid receptor selectively potentiates NMDA-induced outward currents in rat locus coeruleus neurons. Neurosci Res 2008; 60: 22-8.
49. Chen L, Huang LY. Sustained potentiation of NMDA receptormediated glutamate responses through activation of protein kinase C by a m opioid. Neuron 1991; 7: 319-26.
50. Kow LM, Commons KG, Ogawa S, Pfaff DW. Potentiation of the excitatory action of NMDA in ventrolateral periaqueductal gray by the mu-opioid receptor agonist, DAMGO. Brain Res 2002; 935: 87-102.
51. Rusin KI, Randic M. Modulation of NMDA-induced currents by mu-opioid receptor agonist DAGO in acutely isolated rat spinal dorsal horn neurons. Neurosci Lett 1991; 124: 208-12.
52. Martin G, Nie Z, Siggins GR. mu-Opioid receptors modulate NMDA receptor-mediated responses in nucleus accumbens neurons. J Neurosci 1997; 17: 11-22.
53. Przewlocki R, Parsons KL, Sweeney DD, et al. Opioid enhancement of calcium oscillations and burst events involving NMDA receptors and L-type calcium channels in cultured hippocampal neurons. J Neurosci 1999; 19: 9705-15.
54. Elliott K, Minami N, Kolesnikov YA, Pasternak GW, Inturrisi CE. The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the mu-opioid morphine but not to kappa opioids. Pain 1994; 56: 69-75.
55. Herman BH, Vocci F, Bridge P. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction. Neuropsychopharmacology 1995; 13: 269-93.
56. Ben-Eliyahu S, Marek P, Vaccarino AL, et al. The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat. Brain Res 1992; 575: 304-8.
57. Marek P, Ben Eliyahu S, Vaccarino AL, Liebeskind JC. Delayed application of MK-801 attenuates development of morphine tolerance in rats. Brain Res 1991; 558: 163-5.
58. Tanganelli S, Antonelli T, Morari M, Bianchi C, Beani L. Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs. Neurosci Lett 1991; 122: 270-2.
59. Bilsky EJ, Inturrisi CE, Sadee W, Hruby VJ, Porreca F. Competitive and non-competitive NMDA antagonists block the development of antinociceptive tolerance to morphine, but not to selective m or d opioid agonists in mice. Pain 1996; 68: 229-37.
60. Rodríguez-Muñoz M, Torre-Madrid E, Sánchez-Blázquez P, Wang JB, Garzón J. NMDAR-nNOS generated zinc recruits PKCgamma to the HINT1-RGS17 complex bound to the C terminus of Muopioid receptors. Cell Signal 2008; 20: 1855-64.
61. Bonnot A, Corio M, Tramu G, Viala D. Immunocytochemical distribution of ionotropic glutamate receptor subunits in the spinal cord of the rabbit. J Chem Neuroanat 1996; 11: 267-78.
62. Dohrn CS, Beitz AJ. Differential NMDA NR1 mRNA expression among spinal trigeminal neurons that project to different targets. Neuroreport 1994; 5: 1857-60.
63. Petralia RS, Wang YX, Wenthold RJ. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci 1994; 14: 6102-20.
64. Petralia RS, Yokotani N, Wenthold RJ. Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. J Neurosci 1994; 14: 667-96.
65. Tolle TR, Berthele A, Laurie DJ, Seeburg PH, Zieglgansberger W. Cellular and subcellular distribution of NMDAR1 splice variant mRNA in the rat lumbar spinal cord. Eur J Neurosci 1995; 7: 1235-44.
66. Kalb RG, Fox AJ. Synchronized overproduction of AMPA, kainate, and NMDA glutamate receptors during human spinal cord development. J Comp Neurol 1997; 384: 200-10.
67. Wang H, Gracy KN, Pickel VM. Mu-opioid and NMDA-type glutamate receptors are often colocalized in spiny neurons within patches of the caudate-putamen nucleus. J Comp Neurol 1999; 412: 132-46.
68. Gracy KN, Svingos AL, Pickel VM. Dual ultrastructural localization of m-opioid receptors and NMDA-type glutamate receptors in the shell of the rat nucleus accumbens. J Neurosci 1997; 17: 4839-48.
69. Huang J, Wang H, Pickel VM. Rostrocaudal variation in targeting of N-methyl-D-aspartate and mu-opioid receptors in the rat medial nucleus of the solitary tract. J Comp Neurol 2000; 421: 400-11.
70. Glass MJ, Vanyo L, Quimson L, Pickel VM. Ultrastructural relationship between N-methyl-D-aspartate-NR1 receptor subunit and mu-opioid receptor in the mouse central nucleus of the amygdala. Neuroscience 2009; 163: 857-67.
71. Commons KG, van Bockstaele EJ, Pfaff DW. Frequent colocalization of mu opioid and NMDA-type glutamate receptors at postsynaptic sites in periaqueductal gray neurons. J Comp Neurol 1999; 408: 549-59.
72. Kim E, Sheng M. PDZ domain proteins of synapses. Nat Rev Neurosci 2004; 5: 771-81.
73. Sans N, Wang PY, Du Q, et al. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat Cell Biol 2005; 7: 1179-90.
74. Moon IS, Apperson ML, Kennedy MB. The major tyrosinephosphorylated protein in the postsynaptic density fraction is Nmethyl-D-aspartate receptor subunit 2B. Proc Natl Acad Sci U S A 1994; 91: 3954-8.
75. Lau LF, Huganir RL. Differential tyrosine phosphorylation of Nmethyl-D-aspartate receptor subunits. J Biol Chem 1995; 270: 20036-41.
76. Zou X, Lin Q, Willis WD. Effect of protein kinase C blockade on phosphorylation of NR1 in dorsal horn and spinothalamic tract cells caused by intradermal capsaicin injection in rats. Brain Res 2004; 1020: 95-105.
77. Zhang X, Wu J, Lei Y, Fang L, Willis WD. Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following intradermal injection of capsaicin. Brain Res Mol Brain Res 2005; 138: 264-72.
78. Salter MW, Kalia LV. Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci 2004; 5: 317-28.
79. Kalia LV, Salter MW. Interactions between Src family protein tyrosine kinases and PSD-95. Neuropharmacology 2003; 45: 720-8.
80. Lu WY, Xiong ZG, Lei S, et al. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nat Neurosci 1999; 2: 331-8.
81. Sánchez-Blázquez P, Rodríguez-Muñoz M, de la Torre-Madrid E, Garzón J. Brain-specific Gaz interacts with Src tyrosine kinase to regulate Mu-opioid receptor-NMDAR signaling pathway. Cell Signal 2009; 21: 1444-54.
82. Xiong ZG, Raouf R, Lu WY, et al. Regulation of N-methyl-Daspartate receptor function by constitutively active protein kinase C. Mol Pharmacol 1998; 54: 1055-63.
83. Guo W, Wei F, Zou S, et al. Group I metabotropic glutamate receptor NMDA receptor coupling and signaling cascade mediate spinal dorsal horn NMDA receptor 2B tyrosine phosphorylation associated with inflammatory hyperalgesia. J Neurosci 2004; 24: 9161-73.
84. Guo W, Zou S, Guan Y, et al. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J Neurosci 2002; 22: 6208-17.
85. Moriyoshi K, Masu M, Ishii T, et al. Molecular cloning and characterization of the rat NMDA receptor. Nature 1991; 354: 31-7.
86. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994; 12: 529-40.
87. Bhargava HN, Reddy PL, Gudehithlu KP. Down-regulation of Nmethyl-D-aspartate (NMDA) receptors of brain regions and spinal cord of rats treated chronically with morphine. Gen Pharmacol 1995; 26: 131-6.
88. Martin G, Guadano-Ferraz A, Morte B, et al. Chronic morphine treatment alters N-methyl-D-aspartate receptors in freshly isolated neurons from nucleus accumbens. J Pharmacol Exp Ther 2004; 311: 265-73.
89. Bajo M, Crawford EF, Roberto M, Madamba SG, Siggins GR. Chronic morphine treatment alters expression of N-methyl-Daspartate receptor subunits in the extended amygdala. J Neurosci Res 2006; 83: 532-7.
90. Murray F, Harrison NJ, Grimwood S, Bristow LJ, Hutson PH. Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats. Eur J Pharmacol 2007; 562: 191-7.
91. Zhu H, Brodsky M, Gorman AL, Inturrisi CE. Region-specific changes in NMDA receptor mRNA induced by chronic morphine treatment are prevented by the co-administration of the competitive NMDA receptor antagonist LY274614. Brain Res Mol Brain Res 2003; 114: 154-62.
92. Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG. Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 2004; 27: 107-44.
93. 2+-dependent. FEBS Lett 1996; 387: 53-7.
94. Celver JP, Lowe J, Kovoor A, Gurevich VV, Chavkin C. Threonine 180 is required for G-protein-coupled receptor kinase 3-and barrestin 2-mediated desensitization of the m-opioid receptor in Xenopus oocytes. J Biol Chem 2001; 276: 4894-900.
95. Deng HB, Yu Y, Pak Y, et al. Role for the C-terminus in agonistinduced m opioid receptor phosphorylation and desensitization. Biochemistry 2000; 39: 5492-9.
96. 375 residues within the carboxyl tail differentially regulates m-opioid receptor internalization. J Biol Chem 2001; 276: 12774-80.
97. Koch T, Kroslak T, Averbeck M, et al. Allelic variation S268P of the human m-opioid receptor affects both desensitization and G protein coupling. Mol Pharmacol 2000; 58: 328-34.
98. Pak Y, O'Dowd BF, George SR. Agonist-induced desensitization of the m opioid receptor is determined by threonine 394 preceded by acidic amino acids in the COOH-terminal tail. J Biol Chem 1997; 272: 24961-5.
99. Haberstock-Debic H, Kim KA, Yu YJ, von Zastrow M. Morphine promotes rapid, arrestin-dependent endocytosis of m-opioid receptors in striatal neurons. J Neurosci 2005; 25: 7847-57.
100. Keith DE, Anton B, Murray SR, et al. m-Opioid receptor internalization: opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain. Mol Pharmacol 1998; 53: 377-84.
101. Piros ET, Hales TG, Evans CJ. Functional analysis of cloned opioid receptors in transfected cell lines. Neurochem Res 1996; 21: 1277-85.
102. Wang Z, Sadee W. Tolerance to morphine at the m-opioid receptor differentially induced by cAMP-dependent protein kinase activation and morphine. Eur J Pharmacol 2000; 389: 165-71.
103. Granados-Soto V, Kalcheva I, Hua X, Newton A, Yaksh TL. Spinal PKC activity and expression: role in tolerance produced by continuous spinal morphine infusion. Pain 2000; 85: 395-404.
104. Narita M, Narita M, Mizoguchi H, Tseng LF. Inhibition of protein kinase C, but not of protein kinase A, blocks the development of acute antinociceptive tolerance to an intrathecally administered mopioid receptor agonist in the mouse. Eur J Pharmacol 1995; 280: R1-R3.
105. Javed RR, Dewey WL, Smith PA, Smith FL. PKC and PKA inhibitors reverse tolerance to morphine-induced hypothermia and supraspinal analgesia in mice. Eur J Pharmacol 2004; 492: 149-57.
106. Smith FL, Javed RR, Elzey MJ, Dewey WL. The expression of a high level of morphine antinociceptive tolerance in mice involves both PKC and PKA. Brain Res 2003; 985: 78-88.
107. Smith FL, Javed RR, Smith PA, Dewey WL, Gabra BH. PKC and PKA inhibitors reinstate morphine-induced behaviors in morphine tolerant mice. Pharmacol Res 2006; 54: 474-80.
108. Smith FL, Javed R, Elzey MJ, et al. Prolonged reversal of morphine tolerance with no reversal of dependence by protein kinase C inhibitors. Brain Res 2002; 958: 28-35.
109. Inoue M, Ueda H. Protein kinase C-mediated acute tolerance to peripheral m-opioid analgesia in the bradykinin-nociception test in mice. J Pharmacol Exp Ther 2000; 293: 662-9.
110. Narita M, Feng Y, Makimura M, Hoskins B, Ho IK. A protein kinase inhibitor, H-7, inhibits the development of tolerance to opioid antinociception. Eur J Pharmacol 1994; 271: 543-5.
111. Smith FL, Smith PA, Dewey WL, Javed RR. Effects of mGlu1 and mGlu5 metabotropic glutamate antagonists to reverse morphine tolerance in mice. Eur J Pharmacol 2004; 492: 137-42.
112. Nishizuka Y. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J 1995; 9: 484-96.
113. Rodríguez-Muñoz M, Torre-Madrid E, Sánchez-Blázquez P, Garzón J. NO-released zinc supports the simultaneous binding of Raf-1 and PKCgamma cysteine-rich domains to HINT1 protein at the mu-opioid receptor. Antioxid Redox Signal 2011; 14: 2413-25.
114. Korichneva I, Hoyos B, Chua R, Levi E, Hammerling U. Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen. J Biol Chem 2002; 277: 44327-31.
115. Zhao F, Ilbert M, Varadan R, et al. Are zinc-finger domains of protein kinase C dynamic structures that unfold by lipid or redox activation? Antioxid Redox Signal 2011; 14: 757-66.
116. Fontayne A, Dang PM, Gougerot-Pocidalo MA, El-Benna J. Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 2002; 41: 7743-50.
117. Bokoch GM, Diebold B, Kim JS, Gianni D. Emerging evidence for the importance of phosphorylation in the regulation of NADPH oxidases. Antioxid Redox Signal 2009; 11: 2429-41.
118. Knapp LT, Klann E. Superoxide-induced stimulation of protein kinase C via thiol modification and modulation of zinc content. J Biol Chem 2000; 275: 24136-45.
119. Doyle T, Bryant L, Muscoli C, et al. Spinal NADPH oxidase is a source of superoxide in the development of morphine-induced hyperalgesia and antinociceptive tolerance. Neurosci Lett 2010; 483: 85-9.
120. Mao J, Price DD, Phillips LL, Lu J, Mayer DJ. Increases in protein kinase C gamma immunoreactivity in the spinal cord of rats associated with tolerance to the analgesic effects of morphine. Brain Res 1995; 677: 257-67.
121. Malmberg AB, Chen C, Tonegawa S, Basbaum AI. Preserved acute pain and reduced neuropathic pain in mice lacking PKCg. Science 1997; 278: 279-83.
122. Narita M, Mizoguchi H, Suzuki T, et al. Enhanced m-opioid responses in the spinal cord of mice lacking protein kinase Cg isoform. J Biol Chem 2001; 276: 15409-14.
123. Zeitz KP, Malmberg AB, Gilbert H, Basbaum AI. Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKCg mutant mice. Pain 2001; 94: 245-53.
124. Hua XY, Moore A, Malkmus S, et al. Inhibition of spinal protein kinase Ca expression by an antisense oligonucleotide attenuates morphine infusion-induced tolerance. Neuroscience 2002; 113: 99-107.
125. Ventayol P, Busquets X, Garcia-Sevilla JA. Modulation of immunoreactive protein kinase C-a and b isoforms and G proteins by acute and chronic treatments with morphine and other opiate drugs in rat brain. Naunyn Schmiedebergs Arch Pharmacol 1997; 355: 491-500.
126. Smith FL, Gabra BH, Smith PA, Redwood MC, Dewey WL. Determination of the role of conventional, novel and atypical PKC isoforms in the expression of morphine tolerance in mice. Pain 2007; 127: 129-39.
127. Montminy MR, Bilezikjian LM. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 1987; 328: 175-8.
128. Chetkovich DM, Sweatt JD. NMDA receptor activation increases cyclic AMP in area CA1 of the hippocampus via calcium/calmodulin stimulation of adenylyl cyclase. J Neurochem 1993; 61: 1933-42.
129. Lisman JE, Zhabotinsky AM. A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly. Neuron 2001; 31: 191-201.
130. Bradshaw JM, Kubota Y, Meyer T, Schulman H. An ultrasensitive Ca2+/calmodulin-dependent protein kinase II-protein phosphatase 1 switch facilitates specificity in postsynaptic calcium signaling. Proc Natl Acad Sci U S A 2003; 100: 10512-7.
131. Blitzer RD, Connor JH, Brown GP, et al. Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Science 1998; 280: 1940-2.
132. Makhinson M, Chotiner JK, Watson JB, O'Dell TJ. Adenylyl cyclase activation modulates activity-dependent changes in synaptic strength and Ca2+/calmodulin-dependent kinase II autophosphorylation. J Neurosci 1999; 19: 2500-10.
133. Shen J, Benedict GA, Gallagher A, Stafford K, Yoburn BC. Role of cAMP-dependent protein kinase (PKA) in opioid agonist-induced m-opioid receptor downregulation and tolerance in mice. Synapse 2000; 38: 322-7.
134. Bernstein MA, Welch SP. Effects of spinal versus supraspinal administration of cyclic nucleotide-dependent protein kinase inhibitors on morphine tolerance in mice. Drug Alcohol Depend 1997; 44: 41-6.
135. Brüggemann I, Schulz S, Wiborny D, Höllt V. Colocalization of the m-opioid receptor and calcium/calmodulin-dependent kinase II in distinct pain-processing brain regions. Brain Res Mol Brain Res 2000; 85: 239-50.
136. Fukunaga K, Soderling TR, Miyamoto E. Activation of Ca2+/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons. J Biol Chem 1992; 267: 22527-33.
137. Liang D, Li X, Clark JD. Increased expression of Ca2+/calmodulin-dependent protein kinase IIa during chronic morphine exposure. Neuroscience 2004; 123: 769-75.
138. Lou L, Zhou T, Wang P, Pei G. Modulation of Ca2+/calmodulindependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of a and b isoforms. Mol Pharmacol 1999; 55: 557-63.
139. Fan GH, Wang LZ, Qiu HC, Ma L, Pei G. Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence. Mol Pharmacol 1999; 56: 39-45.
140. Lu L, Zeng S, Liu D, Ceng X. Inhibition of the amygdala and hippocampal calcium/calmodulin-dependent protein kinase II attenuates the dependence and relapse to morphine differently in rats. Neurosci Lett 2000; 291: 191-5.
141. 2+/calmodulin-dependent protein kinase II. Eur J Pharmacol 2003; 465: 199-200.
142. Matthews RP, Guthrie CR, Wailes LM, et al. Calcium/calmodulindependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol 1994; 14: 6107-16.
143. Humrich J, Bermel C, Grubel T, Quitterer U, Lohse MJ. Regulation of phosducin-like protein by casein kinase 2 and N-terminal splicing. J Biol Chem 2003; 278: 4474-81.
144. Miles MF, Barhite S, Sganga M, Elliott M. Phosducin-like protein: an ethanol-responsive potential modulator of guanine nucleotidebinding protein function. Proc Natl Acad Sci U S A 1993; 90: 10831-5.
145. Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, de la Torre-Madrid E, Garzón J. Calcium/calmodulin-dependent protein kinase II supports morphine antinociceptive tolerance by phosphorylation of glycosylated phosducin-like protein. Neuropharmacology 2008; 54: 319-30.
146. Chen Y, Sommer C. The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence. Mol Neurobiol 2009; 40: 101-7.
147. Tan M, Groszer M, Tan AM, et al. Phosphoinositide 3-kinase cascade facilitates mu-opioid desensitization in sensory neurons by altering G-protein-effector interactions. J Neurosci 2003; 23: 10292-301.
148. Ma W, Zheng WH, Powell K, Jhamandas K, Quirion R. Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study. Eur J Neurosci 2001; 14: 1091-104.
149. Cui Y, Chen Y, Zhi JL, et al. Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance. Brain Res 2006; 1069: 235-43.
150. Cao JL, He JH, Ding HL, Zeng YM. Activation of the spinal ERK signaling pathway contributes naloxone-precipitated withdrawal in morphine-dependent rats. Pain 2005; 118: 336-49.
151. Bernstein MA, Welch SP. Inhibition of protein phosphatases alters the expression of morphine tolerance in mice. Eur J Pharmacol 1998; 341: 173-7.
152. Mehr SE, Samini M, Namiranian K, et al. Inhibition by immunophilin ligands of morphine-induced tolerance and dependence in guinea pig ileum. Eur J Pharmacol 2003; 467: 205-10.
153. Homayoun H, Khavandgar S, Mehr SE, Namiranian K, Dehpour AR. The effects of FK506 on the development and expression of morphine tolerance and dependence in mice. Behav Pharmacol 2003; 14: 121-7.
154. Komeima K, Hayashi Y, Naito Y, Watanabe Y. Inhibition of neuronal nitric-oxide synthase by calcium/calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells. J Biol Chem 2000; 275: 28139-43.
155. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 2000; 69: 795-827.
156. Turcotte M, Tang W, Ross EM. Coordinate regulation of G protein signaling via dynamic interactions of receptor and GAP. PLoS Comput Biol 2008; 4: e1000148.
157. Tesmer JJ. Structure and function of regulator of G protein signaling homology domains. Prog Mol Biol Transl Sci 2009; 86: 75-113.
158. Garzón J, Rodriguez-Muñoz M, Sánchez-Blázquez P. Morphine alters the selective association between mu-opioid receptors and specific RGS proteins in mouse periaqueductal gray matter. Neuropharmacology 2005; 48: 853-68.
159. Georgoussi Z, Leontiadis L, Mazarakou G, et al. Selective interactions between G protein subunits and RGS4 with the Cterminal domains of the m-and d-opioid receptors regulate opioid receptor signaling. Cell Signal 2006; 18: 771-82.
160. Xie Z, Li Z, Guo L, et al. Regulator of G protein signaling proteins differentially modulate signaling of m and d opioid receptors. Eur J Pharmacol 2007; 565: 45-53.
161. Ballon DR, Flanary PL, Gladue DP, et al. DEP-domain-mediated regulation of GPCR signaling responses. Cell 2006; 126: 1079-93.
162. Guang W, Wang H, Su T, Weinstein IB, Wang JB. Role of mPKCI, a novel mu-opioid receptor interactive protein, in receptor desensitization, phosphorylation, and morphine-induced analgesia. Mol Pharmacol 2004; 66: 1285-92.
163. Ajit SK, Ramineni S, Edris W, et al. RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. Cell Signal 2007; 19: 723-30.
164. Rodríguez-Muñoz M, Sánchez-Blázquez P, Vicente-Sánchez A, et al. The histidine triad nucleotide-binding protein 1 supports muopioid receptor-glutamate NMDA receptor cross-regulation. Cell Mol Life Sci 2011; 68: 2933-49.
165. Garzón J, Rodriguez-Muñoz M, Sánchez-Blázquez P. Do pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery? Curr Drug Abuse Rev 2008; 1: 222-38.
166. Traynor J. mu-Opioid receptors and regulators of G protein signaling (RGS) proteins: From a symposium on new concepts in mu-opioid pharmacology. Drug Alcohol Depend 2012; 121: 173-80.
167. Garnier M, Zaratin PF, Ficalora G, et al. Up-regulation of regulator of G protein signaling 4 expression in a model of neuropathic pain and insensitivity to morphine. J Pharmacol Exp Ther 2003; 304: 1299-306.
168. Garzón J, López-Fando A, Sánchez-Blázquez P. The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mopioid receptors. Neuropsychopharmacology 2003; 28: 1983-90.
169. Sánchez-Blázquez P, Rodríguez-Díaz M, López-Fando A, Rodríguez-Muñoz M, Garzón J. The GBeta5 subunit that associates with the R7 subfamily of RGS proteins regulates mu-opioid effects. Neuropharmacology 2003; 45: 82-95.
170. Xu H, Wang X, Wang J, Rothman RB. Opioid peptide receptor studies. 17. Attenuation of chronic morphine effects after antisense oligodeoxynucleotide knock-down of RGS9 protein in cells expressing the cloned Mu opioid receptor. Synapse 2004; 52: 209-17.
171. Zachariou V, Georgescu D, Sanchez N, et al. Essential role for RGS9 in opiate action. Proc Natl Acad Sci U S A 2003; 100: 13656-61.
172. López-Fando A, Rodríguez-Muñoz M, Sánchez-Blázquez P, Garzón J. Expression of neural RGS-R7 and Gb5 proteins in response to acute and chronic morphine. Neuropsychopharmacology 2005; 30: 99-110.
173. Bouhamdan M, Yan HD, Yan XH, Bannon MJ, Andrade R. Brainspecific regulator of G-protein signaling 9-2 selectively interacts with alpha-actinin-2 to regulate calcium-dependent inactivation of NMDA receptors. J Neurosci 2006; 26: 2522-30.
174. Krupp JJ, Vissel B, Thomas CG, Heinemann SF, Westbrook GL. Interactions of calmodulin and alpha-actinin with the NR1 subunit modulate Ca2+-dependent inactivation of NMDA receptors. J Neurosci 1999; 19: 1165-78.
175. Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P. The RGSZ2 protein exists in a complex with m-opioid receptors and regulates the desensitizing capacity of Gz proteins. Neuropsychopharmacology 2005; 30: 1632-48.
176. Garzón J, Rodríguez-Muñoz M, López-Fando A, García-España A, Sánchez-Blázquez P. RGSZ1 and GAIP regulate m-but not dopioid receptors in mouse CNS: role in tachyphylaxis and acute tolerance. Neuropsychopharmacology 2004; 29: 1091-104.
177. Garzón J, Rodríguez-Muñoz M, Vicente-Sánchez A, et al. RGSZ2 binds to the neural nitric oxide synthase PDZ domain to regulate mu-opioid receptor-mediated potentiation of the N-methyl-Daspartate receptor-calmodulin-dependent protein kinase II pathway. Antioxid Redox Signal 2011; 15: 873-87.
178. Wang J, Tu Y, Woodson J, Song X, Ross EM. A GTPaseactivating protein for the G protein Galphaz. Identification, purification, and mechanism of action. J Biol Chem 1997; 272: 5732-40.
179. Rodríguez-Muñoz M, Bermúdez D, Sánchez-Blázquez P, Garzón J. Sumoylated RGS-Rz proteins act as scaffolds for Mu-opioid receptors and G-protein complexes in mouse brain. Neuropsychopharmacology 2007; 32: 842-50.
180. Garzón J, Rodríguez-Muñoz M, Vicente-Sánchez A, et al. SUMOSIM Interactions Regulate the Activity of RGSZ2 Proteins. PLoS One 2011; 6: e28557.
181. Schulz S, Mayer D, Pfeiffer M, et al. Morphine induces terminal m-opioid receptor desensitization by sustained phosphorylation of serine-375. EMBO J 2004; 23: 3282-9.
182. Rodríguez-Muñoz M, de la Torre-Madrid E, Gaitán G, Sánchez-Blázquez P, Garzón J. RGS14 prevents morphine from internalizing Mu-opioid receptors in periaqueductal gray neurons. Cell Signal 2007; 19: 2558-71.
183. Sánchez-Blázquez P, Rodríguez-Muñoz M, Garzón J. Mu-opioid receptors transiently activate the Akt-nNOS pathway to produce sustained potentiation of PKC-mediated NMDAR-CaMKII signaling. PLoS One 2010; 5: e11278.
184. Willard FS, Willard MD, Kimple AJ, et al. Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector. PLoS One 2009; 4: e4884.
185. Shu FJ, Ramineni S, Hepler JR. RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways. Cell Signal 2010; 22: 366-76.
186. Zhu JJ, Qin Y, Zhao M, Van AL, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 2002; 110: 443-55.
187. Sánchez-Blázquez P, García-España A, Garzón J. In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and supraspinal analgesia evoked by mu and delta opioid agonists. J Pharmacol Exp Ther 1995; 275: 1590-6.
188. Sánchez-Blázquez P, Gómez-Serranillos P, Garzón J. Agonists determine the pattern of G-protein activation in m-opioid receptormediated supraspinal analgesia. Brain Research Bulletin 2001; 54: 229-35.
189. Lima CD, Klein MG, Weinstein IB, Hendrickson WA. Threedimensional structure of human protein kinase C interacting protein 1, a member of the HIT family of proteins. Proc Natl Acad Sci U S A 1996; 93: 5357-62.
190. Pearson JD, DeWald DB, Mathews WR, et al. Amino acid sequence and characterization of a protein inhibitor of protein kinase C. J Biol Chem 1990; 265: 4583-91.
191. McDonald JR, Groschel-Stewart U, Walsh MP. Properties and distribution of the protein inhibitor (Mr 17,000) of protein kinase C. Biochem J 1987; 242: 695-705.
192. Newton AC. Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev 2001; 101: 2353-64.
193. Kroncke KD, Klotz LO. Zinc fingers as biologic redox switches? Antioxid Redox Signal 2009; 11: 1015-27.
194. Tsui J, Inagaki M, Schulman H. Calcium/calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation. J Biol Chem 2005; 280: 9210-6.
195. Korichneva I. Zinc dynamics in the myocardial redox signaling network. Antioxid Redox Signal 2006; 8: 1707-21.
196. 1. Biochemistry 2001; 40: 414-21.
197. Tang W, Tu Y, Nayak SK, et al. Gbg inhibits Ga GTPaseactivating proteins by inhibition of Ga-GTP binding during stimulation by receptor. J Biol Chem 2006; 281: 4746-53.
198. Skiba NP, Hopp JA, Arshavsky VY. The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein. J Biol Chem 2000; 275: 32716-20.
199. Skiba NP, Martemyanov KA, Elfenbein A, et al. RGS9-G beta 5 substrate selectivity in photoreceptors. Opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex. J Biol Chem 2001; 276: 37365-72.
200. Martemyanov KA, Hopp JA, Arshavsky VY. Specificity of G protein-RGS protein recognition is regulated by affinity adapters. Neuron 2003; 38: 857-62.
201. Maret W. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid Redox Signal 2006; 8: 1419-41.
202. Shahani N, Sawa A. Nitric oxide signaling and nitrosative stress in neurons: role for s-nitrosylation. Antioxid Redox Signal 2011; 14: 1493-504.
203. Maret W. The function of zinc metallothionein: a link between cellular zinc and redox state. J Nutr 2000; 130: 1455S-8S.
204. Sánchez-Blázquez P, Rodríguez-Muñoz M, Bailón C, Garzón J. GPCRs promote the release of zinc ions mediated by nNOS/NO and the Redox transducer RGSZ2 protein. Antioxid Redox Signal 2012.
205. Ilbert M, Graf PC, Jakob U. Zinc center as redox switch-new function for an old motif. Antioxid Redox Signal 2006; 8: 835-46.
206. Maret W, Vallee BL. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc Natl Acad Sci U S A 1998; 95: 3478-82.
207. Ali DW, Salter MW. NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity. Curr Opin Neurobiol 2001; 11: 336-42.
208. Chong YP, Ia KK, Mulhern TD, Cheng HC. Endogenous and synthetic inhibitors of the Src-family protein tyrosine kinases. Biochim Biophys Acta 2005; 1754: 210-20.
209. Ma YC, Huang J, Ali S, Lowry W, Huang XY. Src tyrosine kinase is a novel direct effector of G proteins. Cell 2000; 102: 635-46.
210. Thornton C, Yaka R, Dinh S, Ron D. H-Ras modulates N-methyl-D-aspartate receptor function via inhibition of Src tyrosine kinase activity. J Biol Chem 2003; 278: 23823-9.
211. Chakrabarti S, Liu NJ, Gintzler AR. Reciprocal modulation of phospholipase Cb isoforms: adaptation to chronic morphine. Proc Natl Acad Sci U S A 2003; 100: 13686-91.
212. Zheng F, Gingrich MB, Traynelis SF, Conn PJ. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Nat Neurosci 1998; 1: 185-91.
213. Akers RF, Lovinger DM, Colley PA, Linden DJ, Routtenberg A. Translocation of protein kinase C activity may mediate hippocampal long-term potentiation. Science 1986; 231: 587-9.
214. Zheng X, Zhang L, Wang AP, Bennett MV, Zukin RS. Ca2+ influx amplifies protein kinase C potentiation of recombinant NMDA receptors. J Neurosci 1997; 17: 8676-86.
215. Faux MC, Scott JD. Regulation of the AKAP79-protein kinase C interaction by Ca2+/Calmodulin. J Biol Chem 1997; 272: 17038-44.
216. McCullar JS, Larsen SA, Millimaki RA, Filtz TM. Calmodulin is a phospholipase C-b interacting protein. J Biol Chem 2003; 278: 33708-13.
217. McCullar JS, Malencik DA, Vogel WK, et al. Calmodulin potentiates Gbg activation of phospholipase C-b3. Biochem Pharmacol 2007; 73: 270-8.
218. Gerendasy DD, Sutcliffe JG. RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. Mol Neurobiol 1997; 15: 131-63.
219. Wang D, Sadee W, Quillan JM. Calmodulin binding to G proteincoupling domain of opioid receptors. J Biol Chem 1999; 274: 22081-8.
220. 3) in morphine-pretreated cell. J Neurochem 2000; 75: 763-71.
221. Liu M, Yu B, Nakanishi O, Wieland T, Simon M. The Ca2+-dependent binding of calmodulin to an N-terminal motif of the heterotrimeric G protein b subunit. J Biol Chem 1997; 272: 18801-7.
222. Cooper DM. Regulation and organization of adenylyl cyclases and cAMP. Biochem J 2003; 375: 517-29.
223. Westphal RS, Tavalin SJ, Lin JW, et al. Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex. Science 1999; 285: 93-6.
224. Chakrabarti S, Law PY, Loh HH. Distinct differences between morphine-and [D-Ala2, N-MePhe4, Gly-ol5]-enkephalin-mu-opioid receptor complexes demonstrated by cyclic AMP-dependent protein kinase phosphorylation. J Neurochem 1998; 71: 231-9.
225. Yun HY, Gonzalez-Zulueta M, Dawson VL, Dawson TM. Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras. Proc Natl Acad Sci U S A 1998; 95: 5773-8.
226. Kolch W, Heidecker G, Kochs G, et al. Protein kinase C alpha activates RAF-1 by direct phosphorylation. Nature 1993; 364: 249-52.
227. Leicht DT, Balan V, Kaplun A, et al. Raf kinases: function, regulation and role in human cancer. Biochim Biophys Acta 2007; 1773: 1196-212.
228. Arvidsson U, Riedl M, Chakrabarti S, et al. Distribution and targeting of a m-opioid receptor (MOR1) in brain and spinal cord. J Neurosci 1995; 15: 3328-41.
229. Cheng PY, Liu-Chen LY, Pickel VM. Dual ultrastructural immunocytochemical labeling of m and d opioid receptors in the superficial layers of the rat cervical spinal cord. Brain Res 1997; 778: 367-80.
230. Wang HB, Zhao B, Zhong YQ, et al. Coexpression of delta-and mu-opioid receptors in nociceptive sensory neurons. Proc Natl Acad Sci U S A 2010; 107: 13117-22.
231. Gomes I, Gupta A, Filipovska J, et al. A role for heterodimerization of m and d opiate receptors in enhancing morphine analgesia. Proc Natl Acad Sci U S A 2004; 101: 5135-9.
232. Daniels DJ, Lenard NR, Etienne CL, et al. Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series. Proc Natl Acad Sci U S A 2005; 102: 19208-13.
233. 3 cells changes the functional response to m agonists from inhibitory to excitatory. Mol Pharmacol 2003; 63: 89-95.
234. George SR, Fan T, Xie Z, et al. Oligomerization of m-and d-opioid receptors. Generation of novel functional properties. J Biol Chem 2000; 275: 26128-35.
235. Sánchez-Blázquez P, Garzón J. Delta opioid receptor subtypes activate inositol-signaling pathways in the production of antinociception. J Pharmacol Exp Ther 1998; 285: 820-7.
236. Sánchez-Blázquez P, Gómez-Serranillos P, Garzón J. Agonists determine the pattern of G-protein activation in mu-opioid receptor-mediated supraspinal analgesia. Brain Res Bull 2001; 54: 229-35.
237. Traynor JR, Elliott J. d-Opioid receptor subtypes and cross-talk with m-receptors. Trends Pharmacol Sci 1993; 14: 84-6.
238. Abdelhamid EE, Sultana M, Portoghese PS, Takemori AE. Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice. J Pharmacol Exp Ther 1991; 258: 299-303.
239. Fundytus ME, Schiller PW, Shapiro M, Weltrowska G, Coderre TJ. Attenuation of morphine tolerance and dependence with the highly selective d-opioid receptor antagonist TIPP[y]. Eur J Pharmacol 1995; 286: 105-8.
240. Sánchez-Blázquez P, García-España A, Garzón J. Antisense oligodeoxynucleotides to opioid mu and delta receptors reduced morphine dependence in mice: role of delta-2 opioid receptors. J Pharmacol Exp Ther 1997; 280: 1423-31.
241. Zhu Y, King MA, Schuller AG, et al. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in d opioid receptor knockout mice. Neuron 1999; 24: 243-52.
242. 2 [y] produces a potent analgesic effect, no physical dependence, and less tolerance than morphine in rats. J Med Chem 1999; 42: 3520-6.
243. Wells JL, Bartlett JL, Ananthan S, Bilsky EJ. In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid m-agonist/d-antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence. J Pharmacol Exp Ther 2001; 297: 597-605.
244. Cahill CM, Holdridge SV, Morinville A. Trafficking of d-opioid receptors and other G-protein-coupled receptors: implications for pain and analgesia. Trends Pharmacol Sci 2007; 28: 23-31.
245. He SQ, Zhang ZN, Guan JS, et al. Facilitation of mu-opioid receptor activity by preventing delta-opioid receptor-mediated codegradation. Neuron 2011; 69: 120-31.
246. Milan-Lobo L, Whistler JL. Heteromerization of the mu-and deltaopioid receptors produces ligand-biased antagonism and alters mureceptor trafficking. J Pharmacol Exp Ther 2011; 337: 868-75.
247. Xie WY, He Y, Yang YR, et al. Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the delta-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci 2009; 29: 3551-64.
248. Zhang X, Bao L, Guan JS. Role of delivery and trafficking of dopioid peptide receptors in opioid analgesia and tolerance. Trends Pharmacol Sci 2006; 27: 324-9.
249. Liu QR, Zhang PW, Zhen Q, et al. KEPI, a PKC-dependent protein phosphatase 1 inhibitor regulated by morphine. J Biol Chem 2002; 277: 13312-20.
250. Bianchi E, Norcini M, Smrcka A, Ghelardini C. Supraspinal Gbetagamma-dependent stimulation of PLCbeta originating from G inhibitory protein-mu opioid receptor-coupling is necessary for morphine induced acute hyperalgesia. J Neurochem 2009; 111: 171-80.
251. Mathews JL, Smrcka AV, Bidlack JM. A novel Gbg-subunit inhibitor selectively modulates mu-opioid-dependent antinociception and attenuates acute morphine-induced antinociceptive tolerance and dependence. J Neurosci 2008; 28: 12183-9.
252. Kolesnikov YA, Pan YX, Babey AM, et al. Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: evidence for opposing NO actions on morphine analgesia and tolerance. Proc Natl Acad Sci U S A 1997; 94: 8220-5.
253. König C, Gavrilova-Ruch O, von Banchet GS, et al. Modulation of mu opioid receptor desensitization in peripheral sensory neurons by phosphoinositide 3-kinase gamma. Neuroscience 2010; 169: 449-54.
254. Casey PJ, Fong HK, Simon MI, Gilman AG. Gz, a guanine nucleotide-binding protein with unique biochemical properties. J Biol Chem 1990; 265: 2383-90.
255. Garzón J, de la Torre-Madrid E, Rodríguez-Muñoz M, Vicente-Sánchez A, Sánchez-Blázquez P. Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for crosstolerance with morphine. Mol Pain 2009; 5: 11.
256. Ammer H, Christ TE. Identity of adenylyl cyclase isoform determines the G protein mediating chronic opioid-induced adenylyl cyclase supersensitivity. J Neurochem 2002; 83: 818-27.
257. Kim KS, Lee KW, Lee KW, et al. Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. Proc Natl Acad Sci U S A 2006; 103: 3908-13.
258. Garzón J, Castro M, Sánchez-Blazquez P, Sánchez-Blázquez P. Influence of Gz and Gi2 transducer proteins in the affinity of opioid agonists to mu receptors. Eur J Neurosci 1998; 10: 2557-64.
259. Hendry IA, Kelleher KL, Bartlett SE, et al. Hypertolerance to morphine in G(z alpha)-deficient mice. Brain Res 2000; 870: 10-9.
260. Leck KJ, Bartlett SE, Smith MT, et al. Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine. Neuropharmacology 2004; 46: 836-46.
261. Martemyanov KA, Yoo PJ, Skiba NP, Arshavsky VY. R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. J Biol Chem 2005; 280: 5133-6.
262. Marek P, Ben-Eliyahu S, Gold M, Liebeskind JC. Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat. Brain Res 1991; 547: 77-81.
263. Shimoyama N, Shimoyama M, Davis AM, Monaghan DT, Inturrisi CE. An antisense oligonucleotide to the N-methyl-D-aspartate (NMDA) subunit NMDAR1 attenuates NMDA-induced nociception, hyperalgesia, and morphine tolerance. J Pharmacol Exp Ther 2005; 312: 834-40.
264. Richebe P, Cahana A, Rivat C. Tolerance and opioid-induced hyperalgesia. Is a divorce imminent? Pain 2012.
265. Crain SM, Shen KF. Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability. Pain 2000; 84: 121-31.
266. Shen KF, Crain SM. Cholera toxin-B subunit blocks excitatory opioid receptor-mediated hyperalgesic effects in mice, thereby unmasking potent opioid analgesia and attenuating opioid tolerance/dependence. Brain Res 2001; 919: 20-30.
267. 2+/calmodulin-dependent protein kinase II. J Pharmacol Exp Ther 2006; 317: 901-9.
268. Mestek A, Hurley JH, Bye LS, et al. The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci 1995; 15: 2396-406.
269. Narita M, Matsumura Y, Ozaki S, et al. Role of the calcium/calmodulin-dependent protein kinase II (CaMKII) in the morphine-induced pharmacological effects in the mouse. Neuroscience 2004; 126: 415-21.
270. Koch T, Kroslak T, Mayer P, Raulf E, Höllt V. Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonistmediated desensitization. J Neurochem 1997; 69: 1767-70.
271. Rameau GA, Chiu LY, Ziff EB. Bidirectional regulation of neuronal nitric-oxide synthase phosphorylation at serine 847 by the N-methyl-D-aspartate receptor. J Biol Chem 2004; 279: 14307-14.
272. Fundytus ME. Glutamate receptors and nociception: implications for the drug treatment of pain. CNS Drugs 2001; 15: 29-58.
273. Diaz JL, Zamanillo D, Corbera J, et al. Selective s-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem 2009; 9: 172-83.
274. Wang Y, Barker K, Shi S, et al. Blockade of PDGFR-beta activation eliminates morphine analgesic tolerance. Nat Med 2012; 18: 385-7.
275. Nitsche JF, Schuller AG, King MA, et al. Genetic dissociation of opiate tolerance and physical dependence in d-opioid receptor-1 and preproenkephalin knock-out mice. J Neurosci 2002; 22: 10906-13.
276. Bailey CP, Kelly E, Henderson G. Protein kinase C activation enhances morphine-induced rapid desensitization of m-opioid receptors in mature rat locus ceruleus neurons. Mol Pharmacol 2004; 66: 1592-8.
277. Hull LC, Llorente J, Gabra BH, et al. The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy. J Pharmacol Exp Ther 2010; 332: 1127-35.
278. Heinricher MM, Schouten JC, Jobst EE. Activation of brainstem Nmethyl-D-aspartate receptors is required for the analgesic actions of morphine given systemically. Pain 2001; 92: 129-38.
279. Tanowitz M, von Zastrow M. A novel endocytic recycling signal that distinguishes the membrane trafficking of naturally occurring opioid receptors. J Biol Chem 2003; 278: 45978-86.
280. Cox BM, Ginsburg M, Osman OH. Acute tolerance to narcotic analgesic drugs in rats. Br J Pharmacol Chemother 1968; 33: 245-56.
281. Kissin I, Brown PT, Bradley EL, Jr. Magnitude of acute tolerance to opioids is not related to their potency. Anesthesiology 1991; 75: 813-6.
282. Grecksch G, Just S, Pierstorff C, et al. Analgesic tolerance to highefficacy agonists but not to morphine is diminished in phosphorylation-deficient S375A mu-opioid receptor knock-in mice. J Neurosci 2011; 31: 13890-6.
283. Bailey CP, Couch D, Johnson E, et al. Mu-opioid receptor desensitization in mature rat neurons: lack of interaction between DAMGO and morphine. J Neurosci 2003; 23: 10515-20.
284. Sánchez-Blazquez P, Ulibarri I, Garzón J. Intracerebroventricular N-ethylmaleimide differentially reduces supraspinal opioid analgesia in mice. Eur J Pharmacol 1989; 166: 193-200.
285. Garzón J, Martínez-Peña Y, Sánchez-Blazquez P. Dissimilar efficacy of opioids to produce mu-mediated analgesia: role of Gx/z and Gi2 transducer proteins. Life Sci 1994; 55: L205-L212.
286. Garzón J, García-España A, Sánchez-Blazquez P. Opioids binding mu and delta receptors exhibit diverse efficacy in the activation of Gi2 and G(x/z) transducer proteins in mouse periaqueductal gray matter. J Pharmacol Exp Ther 1997; 281: 549-57.
287. Sánchez-Blázquez P, Garzón J. Delta opioid receptor subtypes activate inositol-signaling pathways in the production of antinociception. J Pharmacol Exp Ther 1998; 285: 820-7.
288. Garzón J, Castro M, Sánchez-Blázquez P. Influence of Gz and Gi2 transducer proteins in the affinity of opioid agonists to mu receptors. Eur J Neurosci 1998; 10: 2557-64.
289. Suzuki M. Role of N-methyl-D-aspartate receptor antagonists in postoperative pain management. Curr Opin Anaesthesiol 2009; 22: 618-22.
290. Ingram SL, Traynor JR. Role of protein kinase C in functional selectivity for desensitization at the mu-opioid receptor: from pharmacological curiosity to therapeutic potential. Br J Pharmacol 2009; 158: 154-6.
291. Costantino CM, Gomes I, Stockton SD, Lim MP, Devi LA. Opioid receptor heteromers in analgesia. Expert Rev Mol Med 2012; 14: e9.
292. Bhargava HN. Inhibition of tolerance to the pharmacological effects of human b-endorphin by prolyl-leucyl-glycinamide and cyclo(leucylglycine) in the rat. J Pharmacol Exp Ther 1981; 218: 404-8.
293. Sarnyai Z, Viski S, Krivan M, et al. Endogenous oxytocin inhibits morphine tolerance through limbic forebrain oxytocin receptors. Brain Res 1988; 463: 284-8.
294. Dourish CT, Hawley D, Iversen SD. Enhancement of morphine analgesia and prevention of morphine tolerance in the rat by the cholecystokinin antagonist L-364,718. Eur J Pharmacol 1988; 147: 469-72.
295. Contreras E, Tamayo L, Amigo M. Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance. Eur J Pharmacol 1988; 148: 463-6.
296. Gomaa AA, Mohamed LH, Ahmed HN. Modification of morphineinduced analgesia, tolerance and dependence by bromocriptine. Eur J Pharmacol 1989; 170: 129-35.
297. Lake JR, Hebert KM, Payza K, et al. Analog of neuropeptide FF attenuates morphine tolerance. Neurosci Lett 1992; 146: 203-6.
298. Zarrindast MR, Sajedian M, Rezayat M, Ghazi-Khansari M. Effects of 5-HT receptor antagonists on morphine-induced tolerance in mice. Eur J Pharmacol 1995; 273: 203-7.
299. Azarov AV, Szabo G, Czako L, Telegdy G. Effects of calcitonin gene-related peptide on acute and chronic effects of morphine. Pharmacol Biochem Behav 1995; 52: 595-9.
300. Kolesnikov Y, Jain S, Pasternak GW. Modulation of opioid analgesia by agmatine. Eur J Pharmacol 1996; 296: 17-22.
301. Kreeger JS, Larson AA. The substance P amino-terminal metabolite substance P(1-7), administered peripherally, prevents the development of acute morphine tolerance and attenuates the expression of withdrawal in mice. J Pharmacol Exp Ther 1996; 279: 662-7.
302. Reddy DS, Kulkarni SK. Chronic neurosteroid treatment prevents the development of morphine tolerance and attenuates abstinence behavior in mice. Eur J Pharmacol 1997; 337: 19-25.
303. Raghavendra V, Kulkarni SK. Reversal of morphine tolerance and dependence by melatonin: possible role of central and peripheral benzodiazepine receptors. Brain Res 1999; 834: 178-81.
304. Ueda H, Inoue M, Takeshima H, Iwasawa Y. Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence. J Neurosci 2000; 20: 7640-7.