alpha-neoendorphin and 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)

Topics: Animals; Benzomorphans; Dehydration; Dynorphins; Endorphins; Hypertonic Solutions; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Neurons; Osmolar Concentration; Oxytocin; Peptide Fragments; Pituitary Gland, Posterior; Protein Precursors; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Vasopressins

The levels of dynorphin, alpha-neoendorphin and beta-endorphin immunoreactivity (ir-DYN, ir-alpha-NEO, ir-beta-E) were measured in the brain, pituitary and gut of rats subjected to a variety of manipulations. Water deprivation caused an increase in the ir-DYN and ir-alpha-NEO content in the hypothalamus and a decrease in the neurointermediate (NI) lobe of the pituitary. The ir-beta-E level decreased in the hypothalamus and anterior lobe of the pituitary, while it increased in the NI-pituitary. Food deprivation, as well as chronic fenfluramine (10-20 mg/kg) treatment increased, while acute muscimol (0.5 micrograms/10 microliter) treatment decreased the ir-beta-E, but not ir-DYN or ir-alpha-NEO content in the hypothalamus. The anterior pituitary content of ir-beta-E was increased after food deprivation and decreased after chronic fenfluramine treatment. However, the ir-DYN and ir-alpha-NEO contents in the duodenum were markedly increased after food deprivation, while chronic fenfluramine treatment led to a dramatic decrease in the ir-DYN content. These results suggest that the levels of opioid peptides in the brain, pituitary and gut may be differentially and independently affected by alteration of the ingestive behavior.

Topics: Animals; beta-Endorphin; Dehydration; Duodenum; Dynorphins; Endorphins; Food Deprivation; Hypothalamus; Male; Pituitary Gland; Protein Precursors; Rats; Rats, Inbred Strains; Water Deprivation

Dehydration significantly reduced the concentration of immunoreactive dynorphin A(1-17), dynorphin A(1-8), alpha-neo-endorphin, beta-neo-endorphin, and leu-enkephalin in the rat pituitary posterior-intermediate lobe. A statistically significant increase in immunoreactive dynorphin A(1-8), alpha-neo-endorphin and leu-enkephalin was observed in the hypothalamus. Comparison of the molar ratios of dynorphin A(1-17): dynorphin A(1-8) and alpha-neo-endorphin: beta-neo-endorphin showed an altered profile of stored pro-dynorphin cleavage products in the posterior-intermediate lobe of the pituitary of dehydrated rats.

Topics: Animals; beta-Endorphin; Dehydration; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalins; Food Deprivation; Hypothalamus; Male; Peptide Fragments; Pituitary Gland, Posterior; Protein Precursors; Rats; Rats, Inbred Strains