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 – α- and β-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 neurohypo-physial 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 m/W) were injected intracerebroventricularly I 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 radioimmunossay. After 24 h of water deprivation, the elevation in plasma [OT] but not [VP] was attenuated (p <0.05) by α-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. When administered intracerebroventricularly, both naloxone and the selective kappa receptor antagonist nor-binaltorphimine augmented the rise in plasma OT of rats deprived of water for 24 h. We conclude that dynorphin-related peptides inhibit OT release from magnocellular neurons by a kappa receptor mechanism. Thus, the corelease of a neuromodulator (dynorphin peptides) with the neurohor-mone, VP, could attenuate the inappropriate secretion of OT from adjacent magnocellular neurons during dehydration.
- Mr 2266
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Cellular and Molecular Neuroscience
- Endocrine and Autonomic Systems