?-Opioid Receptors and Not K-Opioid Receptors Are Coupled to the Adenylate Cyclase in the Cerebellum

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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 (>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.