Opioid inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation of rats.
The role of the opioid peptides in the regulation of adrenocorticotropin (ACTH) secretion remains unclear. In rats, morphine and the enkephalins exert a stimulatory effect on the hypothalamic-pituitary-adrenal axis, while beta-endorphin (beta-E) and dynorphin (DYN) are reported to have stimulatory or inhibitory activity. Alternatively, data from human studies indicate a clear inhibitory role of opiates. In the present studies, secretion of immunoreactive corticotropin releasing factor (irCRF) into the hypophysial-portal circulation was directly measured before and after intracerebroventricular administration of beta-E, DYN and naltrexone (NTX). Both beta-E and DYN were equipotent in their dose-related inhibition of irCRF secretion. The inhibitory action of beta-E was reversed by NTX, while the action of DYN was only partially blocked. Administration of NTX alone resulted in a significant elevation of spontaneous and stimulated irCRF secretion. Finally, injection (icv) of 1.0 nmol beta-E or DYN blocked the nitroprusside-hypotension induced elevation of irCRF. These observations suggest, that under the conditions of these experiments, exogenous beta-E acting primarily via mu opioid receptors and DYN acting via kappa and mu receptors exert tonic inhibitory effects on the activity of CRF secreting cells. Furthermore, it appears that beta-E and DYN are capable of modulating (inhibiting) stimulated secretion of irCRF and thus activity of the hypothalamic-pituitary-adrenal axis.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010902:Pituitary Gland / Q000098:blood supply*; D011168:Portal System; D051381:Rats; D011919:Rats, Inbred Strains
D004723:Endorphins; D009599:Nitroprusside; D009271:Naltrexone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone