Naloxone antagonism of corticotropin-releasing hormone stimulation of prolactin secretion in rhesus monkeys.
The effect of opiate receptor blockade on human CRH-induced PRL secretion was examined in ovariectomized and normal female rhesus monkeys. A bolus iv dose of 100 micrograms CRH acutely stimulated PRL secretion in both normal and ovariectomized animals. The magnitude of the PRL response was greater in ovariectomized monkeys (212% increase; n = 5) than in normal monkeys (56% increase; n = 5). Naloxone pretreatment inhibited CRH-induced PRL release in a dose-dependent fashion, whereas nalmefene did not, in both normal and ovariectomized monkeys. Administration of nalmefene alone significantly stimulated PRL secretion in normal monkeys (57% increase; n = 10), but not in ovariectomized monkeys (10% increase; n = 10). Naloxone alone had no effect. Since nalmefene has a high affinity for both the kappa- and mu-receptors whereas naloxone binds primarily to the mu-receptor, these results suggest that CRH-induced PRL secretion in monkeys is mediated by an endogenous opiate which binds to an opiate receptor other than or in addition to the mu- and kappa-receptors.
Vanvugt
D A
DA
Department of Obstetrics and Gynaecology, Queen's University, Kingston, Ontario, Canada.
Webb
M Y
MY
Reid
R L
RL
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008253:Macaca mulatta; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D010052:Ovariectomy; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects; D013997:Time Factors
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; C038981:nalmefene