BETA-ADRENOCEPTOR-SENSITIVE ADENYLATE-CYCLASE IS INHIBITED BY ACTIVATION OF MU-OPIOID RECEPTORS IN RAT STRIATAL NEURONS

The beta-adrenoceptor-sensitive adenylate cyclase in primary cultures of rat striatal neurons was inhibited by opioids, unlike that in rat striatal slices. Isoprenaline (1-mu-M)-stimulated cyclic AMP production was dose dependently inhibited by the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, EC50 = 0.02-mu-M, 36% inhibition), and only slightly reduced by relatively high concentrations of the delta-opioid receptor agonist, [D-penicillamine2,D-penicillamine5]enkephalin (DPDPE, 1-mu-M). The highly selective and potent delta-opioid receptor agonist, [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), and the kappa-opioid receptor agonist, U50-488, were ineffective in concentrations up to 3-mu-M. Naloxone reversed equally well the inhibitory effects of DPDPE and of DAGO, indicating the involvement of functional mu-opioid receptors. The isoprenaline (1-mu-M)-stimulated adenylate cyclase activity in cultured glial cells, which exceeded that in neurons about 10-fold, was not affected by opioids. Therefore, opioids were ineffective in rat brain slices probably due to the fact that cyclic AMP production induced by beta-adrenoceptor activation occurs primarily in the glial cells, where it is not subject to inhibition by opioids. These data indicate for the first time the existence of an interaction between functional mu-opioid receptors and beta-adrenoceptors on striatal neurons of the rat.