title: mu-Opioid receptors and not kappa-opioid receptors are coupled to the adenylate cyclase in the cerebellum.
abstract: The putative regulatory effect of opioids on adenylate cyclase was investigated in two different preparations containing, respectively, two different populations of opioid receptors: the rabbit cerebellum (greater than 75% mu-opioid receptors) and the guinea pig cerebellum (greater than 80% kappa-opioid receptors). In the mu-preparation, but not in the kappa-preparation, opioids inhibited the basal and the forskolin-stimulated adenylate cyclase activity in a dose-dependent manner and stereospecifically. The inhibition was in the 20-30% range, required the presence in the assay medium of Mg2+ and of GTP, but was independent of the presence of Na+. Pharmacological characterization of the inhibitory response in the rabbit cerebellum clearly showed that it was under the control of a mu-opioid binding site, with the effect being elicited by non-selective (etorphine and morphine) and mu-selective (Tyr-D-Ala-Gly-Me-Phe-Gly-ol) agonists, whereas delta- and kappa-selective agonists were almost totally ineffective. ADP ribosylation of inhibitory GTP-binding protein by pertussis toxin failed to block the inhibitory effect of opioids, and data presented suggest that this failure is likely to be the consequence of a limited access of the toxin to its substrate in rabbit cerebellum membranes.
authors: Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS Toulouse, France.
authors: J
authors: J
authors: Polastron
authors: M J
authors: MJ
authors: Boyer
authors: Y
authors: Y
authors: Quertermont
authors: J P
authors: JP
authors: Thouvenot
authors: J C
authors: JC
authors: Meunier
authors: P
authors: P
authors: Jauzac
mesh_terms: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D008566:Membranes / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology; D037342:Pertussis Toxin; D011817:Rabbits; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D009294:Narcotics; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases