Heterodimerization of the kappa opioid receptor and neurotensin receptor 1 contributes to a novel β-arrestin-2–biased pathway

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1863, Issue 11, 2016, Pages 2719-2738

  Liu, Haiqing ^a,b   Tian, Yanjun ^c   Ji, Bingyuan ^c   Lu, Hai ^c   Xin, Qing ^c   Jiang, Yunlu ^c   Ding, Liangcai ^c   Zhang, Jingmei ^c   Chen, Jing ^c,d   Bai, Bo ^c  

^a SHANDONG AGRICULTURAL UNIVERSITY   (China)

^b SHANDONG PROVINCIAL HOSPITAL AFFILIATED TO SHANDONG FIRST MEDICAL UNIVERSITY   (China)

^c JINING MEDICAL UNIVERSITY   (China)

^d UNIVERSITY OF WARWICK   (United Kingdom)

Author keywords

GPCR; Heterodimerization; Kappa opioid receptor; Neurotensin receptor 1

Indexed keywords

BETA ARRESTIN 2; DYNORPHIN; GUANINE NUCLEOTIDE BINDING PROTEIN; HETERODIMER; KAPPA OPIATE RECEPTOR; NEUROTENSIN RECEPTOR; NEUROTENSIN RECEPTOR 1; UNCLASSIFIED DRUG; ARRB2 PROTEIN, HUMAN; ARRB2 PROTEIN, RAT; CYCLIC AMP; DYNORPHIN (1-13); NEUROTENSIN TYPE 1 RECEPTOR; OPRK1 PROTEIN, HUMAN; PEPTIDE FRAGMENT; PROTEIN BINDING;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DIMERIZATION; EMBRYO; FEMALE; HUMAN; HUMAN CELL; MALE; MUTANT; NERVE CELL; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RAT; RECEPTOR OCCUPANCY; SIGNAL TRANSDUCTION; AGONISTS; ANIMAL; BASAL GANGLION; CYTOLOGY; DOSE RESPONSE; DRUG EFFECTS; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; KINETICS; METABOLISM; MUTATION; PRIMARY CELL CULTURE; RNA INTERFERENCE; SPRAGUE DAWLEY RAT;

ANIMALS; ANIMALS, NEWBORN; BASAL GANGLIA; BETA-ARRESTIN 2; CYCLIC AMP; DOSE-RESPONSE RELATIONSHIP, DRUG; DYNORPHINS; FEMALE; HEK293 CELLS; HUMANS; KINETICS; MALE; MUTATION; NEURONS; PEPTIDE FRAGMENTS; PRIMARY CELL CULTURE; PROTEIN BINDING; RATS, SPRAGUE-DAWLEY; RECEPTORS, NEUROTENSIN; RECEPTORS, OPIOID, KAPPA; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSFECTION;

EID: 84983534976     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2016.07.009     Document Type: Article

References (81)

1. [1] Goldstein, A., Tachibana, S., Lowney, L.I., Hunkapiller, M., Hood, L., Dynorphin-(1–13), an extraordinarily potent opioid peptide. Proc. Natl. Acad. Sci. U. S. A. 76 (1979), 6666–6670.
2. [2] Mansour, A., Fox, C.A., Meng, F., Akil, H., Watson, S.J., Kappa 1 receptor mRNA distribution in the rat CNS: comparison to kappa receptor binding and prodynorphin mRNA. Mol. Cell. Neurosci. 5 (1994), 124–144.
3. [3] Waldhoer, M., Bartlett, S.E., Whistler, J.L., Opioid receptors. Annu. Rev. Biochem. 73 (2004), 953–990.
4. [4] Schwarzer, C., 30 years of dynorphins–new insights on their functions in neuropsychiatric diseases. Pharmacol. Ther. 123 (2009), 353–370.
5. [5] Law, P.Y., Wong, Y.H., Loh, H.H., Molecular mechanisms and regulation of opioid receptor signaling. Annu. Rev. Pharmacol. Toxicol. 40 (2000), 389–430.
6. [6] Cox, B.M., Recent developments in the study of opioid receptors. Mol. Pharmacol. 83 (2013), 723–728.
7. [7] Akkuratov, E.E., Lopacheva, O.M., Kruusmagi, M., Lopachev, A.V., Shah, Z.A., Boldyrev, A.A., Liu, L., Functional interaction between Na/K-ATPase and NMDA receptor in cerebellar neurons. Mol. Neurobiol. 52 (2015), 1726–1734.
8. [8] Pfeiffer, A., Brantl, V., Herz, A., Emrich, H.M., Psychotomimesis mediated by kappa opiate receptors. Science (New York, N.Y.) 233 (1986), 774–776.
9. [9] Shippenberg, T.S., Chefer, V.I., Zapata, A., Heidbreder, C.A., Modulation of the behavioral and neurochemical effects of psychostimulants by kappa-opioid receptor systems. Ann. N. Y. Acad. Sci. 937 (2001), 50–73.
10. [10] Bruchas, M.R., Chavkin, C., Kinase cascades and ligand-directed signaling at the kappa opioid receptor. Psychopharmacology 210 (2010), 137–147.
11. [11] Smith, J.S., Schindler, A.G., Martinelli, E., Gustin, R.M., Bruchas, M.R., Chavkin, C., Stress-induced activation of the dynorphin/kappa-opioid receptor system in the amygdala potentiates nicotine conditioned place preference. J. Neurosci. 32 (2012), 1488–1495.
12. [12] Schindler, A.G., Messinger, D.I., Smith, J.S., Shankar, H., Gustin, R.M., Schattauer, S.S., Lemos, J.C., Chavkin, N.W., Hagan, C.E., Neumaier, J.F., Chavkin, C., Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake. J. Neurosci. 32 (2012), 17582–17596.
13. [13] Redila, V.A., Chavkin, C., Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system. Psychopharmacology 200 (2008), 59–70.
14. [14] Waldhoer, M., Fong, J., Jones, R.M., Lunzer, M.M., Sharma, S.K., Kostenis, E., Portoghese, P.S., Whistler, J.L., A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 9050–9055.
15. [15] Schmid, C.L., Streicher, J.M., Groer, C.E., Munro, T.A., Zhou, L., Bohn, L.M., Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at kappa-opioid receptors in striatal neurons. J. Biol. Chem. 288 (2013), 22387–22398.
16. [16] Rives, M.L., Rossillo, M., Liu-Chen, L.Y., Javitch, J.A., 6′-Guanidinonaltrindole (6′-GNTI) is a G protein-biased kappa-opioid receptor agonist that inhibits arrestin recruitment. J. Biol. Chem. 287 (2012), 27050–27054.
17. [17] Fagergren, P., Smith, H.R., Daunais, J.B., Nader, M.A., Porrino, L.J., Hurd, Y.L., Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration. Eur. J. Neurosci. 17 (2003), 2212–2218.
18. [18] Everitt, B.J., Belin, D., Economidou, D., Pelloux, Y., Dalley, J.W., Robbins, T.W., Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 363 (2008), 3125–3135.
19. [19] Milligan, G., G-protein-coupled receptor heterodimers: pharmacology, function and relevance to drug discovery. Drug Discov. Today 11 (2006), 541–549.
20. [20] Ferre, S., The GPCR heterotetramer: challenging classical pharmacology. Trends Pharmacol. Sci. 36 (2015), 145–152.
21. [21] Tena-Campos, M., Ramon, E., Rivera, D., Borroto-Escuela, D.O., Romero-Fernandez, W., Fuxe, K., Garriga, P., G-protein-coupled receptors oligomerization: emerging signaling units and new opportunities for drug design. Curr. Protein Pept. Sci. 15 (2014), 648–658.
22. [22] Kieffer, B.L., Recent advances in molecular recognition and signal transduction of active peptides: receptors for opioid peptides. Cell. Mol. Neurobiol. 15 (1995), 615–635.
23. [23] Kleczkowska, P., Lipkowski, A.W., Neurotensin and neurotensin receptors: characteristic, structure-activity relationship and pain modulation–a review. Eur. J. Pharmacol. 716 (2013), 54–60.
24. [24] Tyler, B.M., Cusack, B., Douglas, C.L., Souder, T., Richelson, E., Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception. Brain Res. 792 (1998), 246–252.
25. [25] Dobner, P.R., Multitasking with neurotensin in the central nervous system. Cell. Mol. Life Sci. CMLS 62 (2005), 1946–1963.
26. [26] Guillemette, A., Dansereau, M.A., Beaudet, N., Richelson, E., Sarret, P., Intrathecal administration of NTS1 agonists reverses nociceptive behaviors in a rat model of neuropathic pain. Eur. J. Pain (London, England) 16 (2012), 473–484.
27. [27] Buhler, A.V., Choi, J., Proudfit, H.K., Gebhart, G.F., Neurotensin activation of the NTR1 on spinally-projecting serotonergic neurons in the rostral ventromedial medulla is antinociceptive. Pain 114 (2005), 285–294.
28. [28] Skoog, K.M., Cain, S.T., Nemeroff, C.B., Centrally administered neurotensin suppresses locomotor hyperactivity induced by D-amphetamine but not by scopolamine or caffeine. Neuropharmacology 25 (1986), 777–782.
29. [29] Mechanic, J.A., Sutton, J.E., Berson, A.E., Wu, X., Kwan, J., Schreiber, R., Pang, Z., Button, D.C., Involvement of the neurotensin receptor 1 in the behavioral effects of two neurotensin agonists, NT-2 and NT69L: lack of hypothermic, antinociceptive and antipsychotic actions in receptor knockout mice. Eur. Neuropsychopharmacol. J. Eur. Coll. Neuropsychopharmacol. 19 (2009), 466–475.
30. [30] Fuxe, K., Borroto-Escuela, D.O., Marcellino, D., Romero-Fernandez, W., Frankowska, M., Guidolin, D., Filip, M., Ferraro, L., Woods, A.S., Tarakanov, A., Ciruela, F., Agnati, L.F., Tanganelli, S., GPCR heteromers and their allosteric receptor-receptor interactions. Curr. Med. Chem. 19 (2012), 356–363.
31. [31] Guo, W., Shi, L., Filizola, M., Weinstein, H., Javitch, J.A., Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer interface determine activation. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 17495–17500.
32. [32] Claude, P.A., Wotta, D.R., Zhang, X.H., Prather, P.L., McGinn, T.M., Erickson, L.J., Loh, H.H., Law, P.Y., Mutation of a conserved serine in TM4 of opioid receptors confers full agonistic properties to classical antagonists. Proc. Natl. Acad. Sci. U. S. A. 93 (1996), 5715–5719.
33. [33] Pappachan, A., Chinnathambi, S., Satheshkumar, P.S., Savithri, H.S., Murthy, M.R., A single point mutation disrupts the capsid assembly in Sesbania Mosaic virus resulting in a stable isolated dimer. Virology 392 (2009), 215–221.
34. [34] Bai, B., Cai, X., Jiang, Y., Karteris, E., Chen, J., Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK(1/2) and cell proliferation via Galphaq-mediated mechanism. J. Cell. Mol. Med. 18 (2014), 2071–2081.
35. [35] Chen, J., Zhang, R., Chen, X., Wang, C., Cai, X., Liu, H., Jiang, Y., Liu, C., Bai, B., Heterodimerization of human orexin receptor 1 and kappa opioid receptor promotes protein kinase A/cAMP-response element binding protein signaling via a Galphas-mediated mechanism. Cell. Signal. 27 (2015), 1426–1438.
36. [36] Li, Y., Chen, J., Bai, B., Du, H., Liu, Y., Liu, H., Heterodimerization of human apelin and kappa opioid receptors: roles in signal transduction. Cell. Signal. 24 (2012), 991–1001.
37. [37] Orsini, M.J., Parent, J.L., Mundell, S.J., Marchese, A., Benovic, J.L., Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the c-terminal tail that mediate receptor internalization. J. Biol. Chem. 274 (1999), 31076–31086.
38. [38] Wang, C., Pan, Y., Zhang, R., Bai, B., Chen, J., Randeva, H.S., Heterodimerization of mouse orexin type 2 receptor variants and the effects on signal transduction. Biochim. Biophys. Acta 1843 (2014), 652–663.
39. [39] Pfleger, K.D., Seeber, R.M., Eidne, K.A., Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nat. Protoc. 1 (2006), 337–345.
40. [40] Pfleger, K.D., Dromey, J.R., Dalrymple, M.B., Lim, E.M., Thomas, W.G., Eidne, K.A., Extended bioluminescence resonance energy transfer (eBRET) for monitoring prolonged protein-protein interactions in live cells. Cell. Signal. 18 (2006), 1664–1670.
41. [41] Lohse, M.J., Nuber, S., Hoffmann, C., Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol. Rev. 64 (2012), 299–336.
42. [42] Parenty, G., Appelbe, S., Milligan, G., CXCR2 chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2-DOP receptor heterodimer. Biochem. J. 412 (2008), 245–256.
43. [43] Bai, B., Tang, J., Liu, H., Chen, J., Li, Y., Song, W., Apelin-13 induces ERK1/2 but not p38 MAPK activation through coupling of the human apelin receptor to the Gi2 pathway. Acta Biochim. Biophys. Sin. 40 (2008), 311–318.
44. [44] Sierra, S., Luquin, N., Rico, A.J., Gomez-Bautista, V., Roda, E., Dopeso-Reyes, I.G., Vazquez, A., Martinez-Pinilla, E., Labandeira-Garcia, J.L., Franco, R., Lanciego, J.L., Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism. Brain Struct. Funct. 220 (2015), 2721–2738.
45. [45] Callen, L., Moreno, E., Barroso-Chinea, P., Moreno-Delgado, D., Cortes, A., Mallol, J., Casado, V., Lanciego, J.L., Franco, R., Lluis, C., Canela, E.I., McCormick, P.J., Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. J. Biol. Chem. 287 (2012), 20851–20865.
46. [46] Jordan, B.A., Devi, L.A., G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399 (1999), 697–700.
47. [47] Manglik, A., Kruse, A.C., Kobilka, T.S., Thian, F.S., Mathiesen, J.M., Sunahara, R.K., Pardo, L., Weis, W.I., Kobilka, B.K., Granier, S., Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 485 (2012), 321–326.
48. [48] Mukherjee, R.S., McBride, E.W., Beinborn, M., Dunlap, K., Kopin, A.S., Point mutations in either subunit of the GABAB receptor confer constitutive activity to the heterodimer. Mol. Pharmacol. 70 (2006), 1406–1413.
49. [49] Rediger, A., Piechowski, C.L., Yi, C.X., Tarnow, P., Strotmann, R., Gruters, A., Krude, H., Schoneberg, T., Tschop, M.H., Kleinau, G., Biebermann, H., Mutually opposite signal modulation by hypothalamic heterodimerization of ghrelin and melanocortin-3 receptors. J. Biol. Chem. 286 (2011), 39623–39631.
50. [50] Bellot, M., Galandrin, S., Boularan, C., Matthies, H.J., Despas, F., Denis, C., Javitch, J., Mazeres, S., Sanni, S.J., Pons, V., Seguelas, M.H., Hansen, J.L., Pathak, A., Galli, A., Senard, J.M., Gales, C., Dual agonist occupancy of AT1-R-alpha2C-AR heterodimers results in atypical Gs-PKA signaling. Nat. Chem. Biol. 11 (2015), 271–279.
51. [51] Smith, K.R., Spector, A.C., The importance of the presence of a 5′-ribonucleotide and the contribution of the T1R1 + T1R3 heterodimer and an additional low-affinity receptor in the taste detection of L-glutamate as assessed psychophysically. J. Neurosci. 34 (2014), 13234–13245.
52. [52] Gonzalez-Maeso, J., Ang, R.L., Yuen, T., Chan, P., Weisstaub, N.V., Lopez-Gimenez, J.F., Zhou, M., Okawa, Y., Callado, L.F., Milligan, G., Gingrich, J.A., Filizola, M., Meana, J.J., Sealfon, S.C., Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452 (2008), 93–97.
53. [53] Guo, W., Urizar, E., Kralikova, M., Mobarec, J.C., Shi, L., Filizola, M., Javitch, J.A., Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J. 27 (2008), 2293–2304.
54. [54] Borroto-Escuela, D.O., Marcellino, D., Narvaez, M., Flajolet, M., Heintz, N., Agnati, L., Ciruela, F., Fuxe, K., A serine point mutation in the adenosine A2AR C-terminal tail reduces receptor heteromerization and allosteric modulation of the dopamine D2R. Biochem. Biophys. Res. Commun. 394 (2010), 222–227.
55. [55] Borroto-Escuela, D.O., Romero-Fernandez, W., Tarakanov, A.O., Gomez-Soler, M., Corrales, F., Marcellino, D., Narvaez, M., Frankowska, M., Flajolet, M., Heintz, N., Agnati, L.F., Ciruela, F., Fuxe, K., Characterization of the A2AR-D2R interface: focus on the role of the C-terminal tail and the transmembrane helices. Biochem. Biophys. Res. Commun. 402 (2010), 801–807.
56. [56] Rajagopal, S., Rajagopal, K., Lefkowitz, R.J., Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat. Rev. Drug Discov. 9 (2010), 373–386.
57. [57] Wei, H., Ahn, S., Shenoy, S.K., Karnik, S.S., Hunyady, L., Luttrell, L.M., Lefkowitz, R.J., Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc. Natl. Acad. Sci. U. S. A. 100 (2003), 10782–10787.
58. [58] Rajagopal, K., Whalen, E.J., Violin, J.D., Stiber, J.A., Rosenberg, P.B., Premont, R.T., Coffman, T.M., Rockman, H.A., Lefkowitz, R.J., Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 16284–16289.
59. [59] Rozenfeld, R., Devi, L.A., Exploring a role for heteromerization in GPCR signalling specificity. Biochem. J. 433 (2011), 11–18.
60. [60] George, S.R., Fan, T., Xie, Z., Tse, R., Tam, V., Varghese, G., O'Dowd, B.F., Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties. J. Biol. Chem. 275 (2000), 26128–26135.
61. [61] Gomes, I., Gupta, A., Filipovska, J., Szeto, H.H., Pintar, J.E., Devi, L.A., A role for heterodimerization of mu and delta opiate receptors in enhancing morphine analgesia. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 5135–5139.
62. [62] Fan, T., Varghese, G., Nguyen, T., Tse, R., O'Dowd, B.F., George, S.R., A role for the distal carboxyl tails in generating the novel pharmacology and G protein activation profile of mu and delta opioid receptor hetero-oligomers. J. Biol. Chem. 280 (2005), 38478–38488.
63. [63] Hasbi, A., Nguyen, T., Fan, T., Cheng, R., Rashid, A., Alijaniaram, M., Rasenick, M.M., O'Dowd, B.F., George, S.R., Trafficking of preassembled opioid mu-delta heterooligomer-Gz signaling complexes to the plasma membrane: coregulation by agonists. Biochemistry 46 (2007), 12997–13009.
64. [64] Rozenfeld, R., Devi, L.A., Receptor heterodimerization leads to a switch in signaling: beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 21 (2007), 2455–2465.
65. [65] Violin, J.D., Lefkowitz, R.J., Beta-arrestin-biased ligands at seven-transmembrane receptors. Trends Pharmacol. Sci. 28 (2007), 416–422.
66. [66] Gesty-Palmer, D., Chen, M., Reiter, E., Ahn, S., Nelson, C.D., Wang, S., Eckhardt, A.E., Cowan, C.L., Spurney, R.F., Luttrell, L.M., Lefkowitz, R.J., Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J. Biol. Chem. 281 (2006), 10856–10864.
67. [67] McLennan, G.P., Kiss, A., Miyatake, M., Belcheva, M.M., Chambers, K.T., Pozek, J.J., Mohabbat, Y., Moyer, R.A., Bohn, L.M., Coscia, C.J., Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways. J. Neurochem. 107 (2008), 1753–1765.
68. [68] Rashid, A.J., So, C.H., Kong, M.M., Furtak, T., El-Ghundi, M., Cheng, R., O'Dowd, B.F., George, S.R., D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 654–659.
69. [69] Fonseca, J.M., Lambert, N.A., Instability of a class a G protein-coupled receptor oligomer interface. Mol. Pharmacol. 75 (2009), 1296–1299.
70. [70] Hermans, E., Octave, J.N., Maloteaux, J.M., Receptor mediated internalization of neurotensin in transfected Chinese hamster ovary cells. Biochem. Pharmacol. 47 (1994), 89–91.
71. [71] Reiter, E., Ahn, S., Shukla, A.K., Lefkowitz, R.J., Molecular mechanism of beta-arrestin-biased agonism at seven-transmembrane receptors. Annu. Rev. Pharmacol. Toxicol. 52 (2012), 179–197.
72. [72] Shenoy, S.K., Lefkowitz, R.J., Beta-arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol. Sci. 32 (2011), 521–533.
73. [73] Schmid, C.L., Bohn, L.M., Physiological and pharmacological implications of beta-arrestin regulation. Pharmacol. Ther. 121 (2009), 285–293.
74. [74] Raehal, K.M., Bohn, L.M., Mu opioid receptor regulation and opiate responsiveness. AAPS J. 7 (2005), E587–E591.
75. [75] Bruns, I.R., Chhum, S., Dinh, A.T., Doerr, H., Dunn, N.R., Ly, Y.T., Mitman, C.L., Rickards, H.D., Sol, C., Wan, E.W., Raffa, R.B., A potential novel strategy to separate therapeutic- and side-effects that are mediated via the same receptor: beta-arrestin2/G-protein coupling antagonists. J. Clin. Pharm. Ther. 31 (2006), 119–128.
76. [76] Chavkin, C., The therapeutic potential of kappa-opioids for treatment of pain and addiction. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 36 (2011), 369–370.
77. [77] Wang, X.M., Zhou, Y., Spangler, R., Ho, A., Han, J.S., Kreek, M.J., Acute intermittent morphine increases preprodynorphin and kappa opioid receptor mRNA levels in the rat brain. Brain Res. Mol. Brain Res. 66 (1999), 184–187.
78. [78] Unterwald, E.M., Rubenfeld, J.M., Kreek, M.J., Repeated cocaine administration upregulates kappa and mu, but not delta, opioid receptors. Neuroreport 5 (1994), 1613–1616.
79. [79] Gupta, A., Mulder, J., Gomes, I., Rozenfeld, R., Bushlin, I., Ong, E., Lim, M., Maillet, E., Junek, M., Cahill, C.M., Harkany, T., Devi, L.A., Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci. Signal., 3, 2010 (ra54).
80. [80] Walsh, S.L., Geter-Douglas, B., Strain, E.C., Bigelow, G.E., Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans. J. Pharmacol. Exp. Ther. 299 (2001), 147–158.
81. [81] He, S.Q., Zhang, Z.N., Guan, J.S., Liu, H.R., Zhao, B., Wang, H.B., Li, Q., Yang, H., Luo, J., Li, Z.Y., Wang, Q., Lu, Y.J., Bao, L., Zhang, X., Facilitation of mu-opioid receptor activity by preventing delta-opioid receptor-mediated codegradation. Neuron 69 (2011), 120–131.