title: BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates.
abstract: The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB(2) and CB(1) receptors, respectively. In HEK-293 cells stably expressing the human CB(2) receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB(2) receptor can interact productively with 16z44, a promiscuous G alpha(16/z) chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB(2) receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB(2) receptor acting via G alpha(i/o) and G alpha(q) family-coupled pathways.
authors.affiliation: Department of Biochemistry, Molecular Neuroscience Center, and Biotechnology Research Institute, Hong Kong University of Science and Technology, Clearwater Bay, Hong Kong, PR China.
authors.forename: David C
authors.initials: DC
authors.lastname: New
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism*; D008024:Ligands; D009025:Morpholines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D015290:Second Messenger Systems
chemical_list: D007295:Inositol Phosphates; D008024:Ligands; D009025:Morpholines; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C471852:indomethacin morpholinylamide; D005576:Colforsin; C103505:AM 251; D000242:Cyclic AMP; D007213:Indomethacin