Functional selectivity of CB2 cannabinoid receptor ligands at a canonical and noncanonical pathways

Journal of Pharmacology and Experimental Therapeutics

Volumn 358, Issue 2, 2016, Pages 342-351

  Dhopeshwarkar, Amey ^a   Mackie, Ken ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 DEOXY 3 (1,1 DIMETHYLBUTYL) DELTA8 TETRAHYDROCANNABINOL; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 4 [4 (1,1 DIMETHYLHEPTYL) 2,6 DIMETHOXYPHENYL] 6,6 DIMETHYLBICYCLO[3.1.1]HEPT 2 EN 2 YLMETHANOL; 6 IODO 3 (4 METHOXYBENZOYL) 2 METHYL 1 (2 MORPHOLINOETHYL)INDOLE; ADENYLATE CYCLASE; AM 1710; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR AGONIST; GUANINE NUCLEOTIDE BINDING PROTEIN; GW 833972A; JTE 907; KM 233; L 759633; L 759656; RETINA S ANTIGEN; SR 144258; STS 135; TETRAHYDROCANNABINOL; UNCLASSIFIED DRUG; UR 144; ADENYLATE CYCLASE INHIBITOR; LIGAND;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; DRUG TARGETING; ENZYME ASSAY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; DOSE RESPONSE; DRUG EFFECTS; ENZYME SPECIFICITY; HEK293 CELL LINE; METABOLISM;

ADENYLYL CYCLASE INHIBITORS; ADENYLYL CYCLASES; ARRESTIN; DOSE-RESPONSE RELATIONSHIP, DRUG; HEK293 CELLS; HUMANS; LIGANDS; RECEPTOR, CANNABINOID, CB2; SIGNAL TRANSDUCTION; SUBSTRATE SPECIFICITY;

EID: 84979074731     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.116.232561     Document Type: Article

References (57)

1. Abadji V, Lucas-Lenard JM, Chin C, and Kendall DA (1999) Involvement of the carboxyl terminus of the third intracellular loop of the cannabinoid CB1 receptor in constitutive activation of Gs. J Neurochem 72:2032-2038.
2. Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, McGrath JC, Catterall WA, Spedding M, Peters JA, and Harmar AJ, et al.; CGTP Collaborators (2013) The Concise Guide to Pharmacology 2013/14: overview. Br J Pharmacol 170: 1449-1458.
3. Atwood BK, Straiker A, and Mackie K (2012a) CB? cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. Neuropharmacology 63:514-523.
4. Atwood BK, Wager-Miller J, Haskins C, Straiker A, and Mackie K (2012b) Functional selectivity in CB2 cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB2 ligands. Mol Pharmacol 81:250-263.
5. Bayewitch M, Avidor-Reiss T, Levy R, Barg J, Mechoulam R, and Vogel Z (1995) The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling. FEBS Lett 375:143-147.
6. Blättermann S, Peters L, Ottersbach PA, Bock A, Konya V, Weaver CD, Gonzalez A, Schroder R, Tyagi R, and Luschnig P, et al. (2012) A biased ligand for OXE-R uncouples Ga and Gbg signaling within a heterotrimer. Nat Chem Biol 8:631-638.
7. Bolognini D, Cascio MG, Parolaro D, and Pertwee RG (2012) AM630 behaves as a protean ligand at the human cannabinoid CB2 receptor. Br J Pharmacol 165: 2561-2574.
8. Bouaboula M, Dussossoy D, and Casellas P (1999) Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses. J Biol Chem 274:20397-20405.
9. Bouaboula M, Poinot-Chazel C, Marchand J, Canat X, Bourrié B, Rinaldi-Carmona M, Calandra B, Le Fur G, and Casellas P (1996) Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-Activated protein kinase and induction of Krox-24 expression. Eur J Biochem 237:704-711.
10. Cabral GA and Griffin-Thomas L (2009) Emerging role of the CB2 cannabinoid receptor in immune regulation and therapeutic prospects. Expert Rev Mol Med 11:e3.
11. Calandra B, Portier M, Kernéis A, Delpech M, Carillon C, Le Fur G, Ferrara P, and Shire D (1999) Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor. Eur J Pharmacol 374:445-455.
12. Console-Bram L, Marcu J, and Abood ME (2012) Cannabinoid receptors: nomenclature and pharmacological principles. Prog Neuropsychopharmacol Biol Psychiatry 38:4-15.
13. Deng L, Guindon J, Cornett BL, Makriyannis A, Mackie K, and Hohmann AG (2015) Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal. Biol Psychiatry 77: 475-487.
14. DeWire SM, Ahn S, Lefkowitz RJ, and Shenoy SK (2007) Beta-Arrestins and cell signaling. Annu Rev Physiol 69:483-510.
15. Dhopeshwarkar A and Mackie K (2014) CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Mol Pharmacol 86:430-437.
16. Ehrhart J, Obregon D, Mori T, Hou H, Sun N, Bai Y, Klein T, Fernandez F, Tan J, and Shytle RD (2005) Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J Neuroinflammation 2:29.
17. Evans BA, Broxton N, Merlin J, Sato M, Hutchinson DS, Christopoulos A, and Summers RJ (2011) Quantification of functional selectivity at the human a1Aadrenoceptor. Mol Pharmacol 79:298-307.
18. Flores-Otero J, Ahn KH, Delgado-Peraza F, Mackie K, Kendall DA, and Yudowski GA (2014) Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1. Nat Commun 5:4589.
19. Franklin JM, Vasiljevik T, Prisinzano TE, and Carrasco GA (2013) Cannabinoid agonists increase the interaction between b-Arrestin 2 and ERK1/2 and upregulate b-Arrestin 2 and 5-HT2A receptors. Pharmacol Res 68:46-58.
20. Glass M and Felder CC (1997) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 17:5327-5333.
21. Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, and Hipkin RW (2000) Endocannabinoid 2-Arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol 57:1045-1050.
22. Gudermann T, Schöneberg T, and Schultz G (1997) Functional and structural complexity of signal transduction via G-protein-coupled receptors. Annu Rev Neurosci 20:399-427.
23. Guillot A, Hamdaoui N, Bizy A, Zoltani K, Souktani R, Zafrani ES, Mallat A, Lotersztajn S, and Lafdil F (2014) Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver. Hepatology 59:296-306.
24. Herrera B, Carracedo A, Diez-Zaera M, Gómez del Pulgar T, Guzmán M, and Velasco G (2006) The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Exp Cell Res 312:2121-2131.
25. Herrera B, Carracedo A, Diez-Zaera M, Guzmán M, and Velasco G (2005) p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells. FEBS Lett 579:5084-5088.
26. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, DevaneWA, Felder CC, Herkenham M, Mackie K, and Martin BR, et al. (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161-202.
27. Ignatowska-Jankowska BM, Muldoon PP, Lichtman AH, and Damaj MI (2013) The cannabinoid CB2 receptor is necessary for nicotine-conditioned place preference, but not other behavioral effects of nicotine in mice. Psychopharmacology (Berl) 229:591-601.
28. Kenakin T (1987) Agonists, partial agonists, antagonists, inverse agonists and agonist/antagonists? Trends Pharmacol Sci 8:423-426.
29. Kenakin T (2002) Efficacy at G-protein-coupled receptors. Nat Rev Drug Discov 1: 103-110.
30. Kenakin T (2011) Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther 336:296-302.
31. Kenakin T and Christopoulos A (2013) Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov 12:205-216.
32. Kenakin T, Watson C, Muniz-Medina V, Christopoulos A, and Novick S (2012) A simple method for quantifying functional selectivity and agonist bias. ACS Chem Neurosci 3:193-203.
33. Lauckner JE, Hille B, and Mackie K (2005) The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc Natl Acad Sci USA 102:19144-19149.
34. Luttrell LM and Lefkowitz RJ (2002) The role of b-Arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455-465.
35. McAllister SD, Griffin G, Satin LS, and Abood ME (1999) Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a Xenopus oocyte expression system. J Pharmacol Exp Ther 291:618-626.
36. McGuinness D, Malikzay A, Visconti R, Lin K, Bayne M, Monsma F, and Lunn CA (2009) Characterizing cannabinoid CB2 receptor ligands using DiscoveRx Path-HunterTM b-Arrestin assay. J Biomol Screen 14:49-58.
37. Molina-Holgado E, Vela JM, Arévalo-Martín A, Almazán G, Molina-Holgado F, Borrell J, and Guaza C (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22:9742-9753.
38. Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, Perchuk A, Mora Z, Tagliaferro PA, and Gardner E, et al. (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS One 3: e1640.
39. Pacher P and Haskó G (2008) Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 153:252-262.
40. Pertwee RG (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129-180.
41. Pertwee RG (2007) Cannabinoids and multiple sclerosis. Mol Neurobiol 36:45-59.
42. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, and Mackie K, et al. (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB? and CB?. Pharmacol Rev 62:588-631.
43. Rajagopal S, Ahn S, Rominger DH, Gowen-MacDonald W, Lam CM, Dewire SM, Violin JD, and Lefkowitz RJ (2011) Quantifying ligand bias at seventransmembrane receptors. Mol Pharmacol 80:367-377.
44. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F, Makriyannis A, and Pertwee RG (1999) Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630. Br J Pharmacol 126:665-672.
45. Schuehly W, Paredes JM, Kleyer J, Huefner A, Anavi-Goffer S, Raduner S, Altmann KH, and Gertsch J (2011) Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB2 receptor inverse agonists. Chem Biol 18: 1053-1064.
46. Shoemaker JL, Ruckle MB, Mayeux PR, and Prather PL (2005) Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J Pharmacol Exp Ther 315:828-838.
47. Shoemaker JL, Seely KA, Reed RL, Crow JP, and Prather PL (2007) The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J Neurochem 101: 87-98.
48. Smrcka AV (2008) G protein bg subunits: central mediators of G protein-coupled receptor signaling. Cell Mol Life Sci 65:2191-2214.
49. Sugiura T, Kondo S, Kishimoto S, Miyashita T, Nakane S, Kodaka T, Suhara Y, Takayama H, and Waku K (2000) Evidence that 2-Arachidonoylglycerol but not Npalmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells. J Biol Chem 275:605-612.
50. Turu G and Hunyady L (2010) Signal transduction of the CB1 cannabinoid receptor. J Mol Endocrinol 44:75-85.
51. Valant C, May LT, Aurelio L, Chuo CH, White PJ, Baltos JA, Sexton PM, Scammells PJ, and Christopoulos A (2014) Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. Proc Natl Acad Sci USA 111:4614-4619.
52. van der Lee MM, Blomenröhr M, van der Doelen AA, Wat JW, Smits N, Hanson BJ, van Koppen CJ, and Zaman GJ (2009) Pharmacological characterization of receptor redistribution and b-Arrestin recruitment assays for the cannabinoid receptor 1. J Biomol Screen 14:811-823.
53. van der Westhuizen ET, Breton B, Christopoulos A, and Bouvier M (2014) Quantification of ligand bias for clinically relevant b2-Adrenergic receptor ligands: implications for drug taxonomy. Mol Pharmacol 85:492-509.
54. Wisler JW, DeWire SM, Whalen EJ, Violin JD, Drake MT, Ahn S, Shenoy SK, and Lefkowitz RJ (2007) A unique mechanism of b-blocker action: carvedilol stimulates b-Arrestin signaling. Proc Natl Acad Sci USA 104:16657-16662.
55. Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ, Bi GH, Li J, and Gardner EL (2011) Brain cannabinoid CB? receptors modulate cocaine's actions in mice. Nat Neurosci 14:1160-1166.
56. Zheng H, Chu J, Qiu Y, Loh HH, and Law PY (2008) Agonist-selective signaling is determined by the receptor location within the membrane domains. Proc Natl Acad Sci USA 105:9421-9426.
57. Zheng H, Chu J, Zhang Y, Loh HH, and Law PY (2011) Modulating m-opioid receptor phosphorylation switches agonist-dependent signaling as reflected in PKC activation and dendritic spine stability. J Biol Chem 286:12724-12733.