MU-OPIOID RECEPTORS AND NOT KAPPA-OPIOID RECEPTORS ARE COUPLED TO THE ADENYLATE-CYCLASE IN THE CEREBELLUM

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 (>75%μ‐opioid receptors) and the guinea pig cerebellum (>80%K‐opioid receptors). In the μ‐preparation, but not in the K‐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 μ‐opioid binding site, with the effect being elicited by nonselective (etorphine and morphine) and μ‐selective (Tyr‐D‐Ala‐Gly‐Me‐Phe‐Gly‐ol) agonists, whereas δ‐ and K‐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. Copyright © 1990, Wiley Blackwell. All rights reserved