Kappa opiate receptors inhibit release of oxytocin from the magnocellular system during dehydration.
Magnocellular neurons synthesize vasopressin (VP) or oxytocin (OT) and release these hormones preferentially from the neural lobe during physiological stimulation. In the rat, VP is secreted preferentially during dehydration and hemorrhage, whereas OT is released without VP by suckling, parturition, stress, and nausea. Vasopressinergic neurons also synthesize and release dynorphin-related peptides--alpha- and beta-neoendorphin, dynorphin A (1-8) or (1-17), dynorphin B--which are agonists selective for kappa opiate receptors in the neural lobe. We proposed that one mechanism for preferential secretion of neurohypophysial hormones is that a dynorphin-related peptide(s) coreleased with VP inhibits selectively OT secretion from magnocellular neurons. We tested this hypothesis in conscious adult male Sprague-Dawley rats which were stimulated by either hypertonic saline administered intraperitoneally (2.5%, 20 ml/kg) or subcutaneously (1 M, 15 ml/kg) or by 24 h of water deprivation. Two approaches were used: (1) dynorphin-related peptides (0.02-20.4 mM) were injected intracerebroventricularly 1 min before decapitating the animal, and (2) the action of endogenous opioid peptides was blocked by injecting subcutaneously or intracerebroventricularly either naloxone or a selective kappa receptor antagonist, Mr 2266 or nor-binaltorphimine. VP and OT were measured by radioimmunoassay. After 24 h of water deprivation, the elevation in plasma [OT] but not [VP] was attenuated (p less than 0.05) by alpha-neoendorphin. Dynorphin A (1-8) also inhibited the release of OT and not VP after intraperitoneal administration of hypertonic saline. Blocking the action of endogenous opioid peptides at kappa receptors with Mr 2266 given peripherally (s.c.) elevated plasma [OT] but not [VP] after stimulation with hypertonic saline administered intraperitoneally or subcutaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
Summy-Long
J Y
JY
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey.
Rosella-Dampman
L M
LM
McLemore
G L
GL
Koehler
E
E
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003681:Dehydration / Q000378:metabolism / Q000503:physiopathology*; D004399:Dynorphins / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D006982:Hypertonic Solutions; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009994:Osmolar Concentration; D010121:Oxytocin / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D014667:Vasopressins / Q000378:metabolism
D001575:Benzomorphans; D004723:Endorphins; D006982:Hypertonic Solutions; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D011498:Protein Precursors; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D014667:Vasopressins; D009270:Naloxone; C051844:norbinaltorphimine; D010121:Oxytocin; C027247:MR 2266; D009271:Naltrexone; C025681:alpha-neoendorphin; D004399:Dynorphins; C026770:dynorphin (1-8)