Enkephalin and opiate narcotics increase cyclic GMP accumulation in slices of rat neostriatum

SEVERAL recent studies suggest that cyclic nucleotides are involved in the cellular actions of the opiate narcotics1–5. Following the observation by Collier and Roy1 that low concentrations of morphine inhibited prostaglandin E1 (PGE1)-stimulated adenylate cyclase activity in rat brain, Traber et al.2 showed that morphine acted similarly to block the rise in intracellular 3′,5′-adenosine monophosphate (cyclic AMP) induced by PGE1 in cultured neuroblastoma, or in a hybrid cell line of neuroblastoma×glioma with a high density of opiate receptor binding sites. Sharma et al.3 found that morphine inhibited basal adenylate cyclase activity in this cell line and Gullis et al.4 observed that morphine increased the 3′,5′-guanosine monophosphate (cyclic GMP) and reduced the cyclic AMP content of these cells. Racagni et al.5have also demonstrated that injection of analgesic doses of morphine in vivo to rats also increased cyclic GMP concentration in the neostriatum. These effects have generally been found to be stereospecific and blocked by the opiate receptor antagonist drug naloxone, suggesting that they are mediated through specific opiate receptors. We have extended these observations to in vitro studies on slices of rat neostriatum, an area with a very high density of opiate receptor binding sites6, and have also examined the effects of enkephalin on this system.