Identification of multiple opiate receptors through neuroendocrine responses. I. Effects of agonists

The effects of the systemic administration of three prototypic multiple opiate receptor agonists, morphine sulfate (MS), ethylketocyclazocine methanesulfonate (EKC) and N-allylnormetazocine hydrochloride (NANMT), on the release of anterior pituitary hormones were studied in the rat. The serum levels of corticosterone, growth hormone, prolactin and luteinizing hormone were measured by radioimmunoassay 30 min after s.c. injection of the drugs. The three opiate compounds elicited different patterns of release of the four hormones. MS, EKC and NANMT elicited rises in the serum levels of corticosterone whereas only MS and EKC induced elevations in growth hormone. MS stimulated but NANMT inhibited the release of prolactin. The administration of the lowest dose of EKC stimulated the release of prolactin whereas higher doses were without effect suggesting biphasic dose-response relationship. The administration of MS, EKC and the highest dose of NANMT elicited a fall in serum luteinizing hormone levels suggesting that NANMT possesses agonist activity at the receptor mediating luteinizing hormone release. The data support the hypothesis that multiple opiate receptors are involved in the mechanism of action of opiate-induced changes in anterior pituitary hormone release.