dynorphins and Dehydration

Salt-loading induces profound metabolic changes in magnocellular vasopressin (AVP)-containing neurons, including changes in levels of coexisting peptides and tyrosine hydroxylase (TH). Although many studies have been conducted on salt-loading, little information is available on the recovery processes following its cessation. In the present study, we investigated the changes in AVP, galanin (Gal), dynorphin B (Dyn-B), and TH immunoreactivities in the rat supraoptic nucleus (SON) and paraventricular nucleus (PVN) by immunocytochemistry using specific antisera against these substances. Salt-loading was induced in rats by dissolving 2% NaCl in their drinking water for 7 days. These animals were then allowed free access to fresh water for 2, 4, or 7 days prior to sacrifice. In the SON at the 7th day of salt-loading, AVP, Gal and Dyn-B immunoreactivities decreased in contrast to the marked increase in TH-immunoreactivity compared to those of control rats with free access to water. After a recovery period with free access to water, AVP and Gal immunoreactivities increased with time and returned to the control level at the 7th day. However, Dyn-B immunoreactivity did not recover even at the 7th day. Dehydration-induced TH-immunoreactive neurons almost disappeared at the 7th day. Immunoreactivities for these substances in the PVN showed a similar time course as that in the SON. These findings suggest that AVP and substances coexisting with it change with different time courses in magnocellular neurons following cessation of salt-loading.

Topics: Animals; Arginine Vasopressin; Dehydration; Dynorphins; Fluid Therapy; Galanin; Immunohistochemistry; Male; Paraventricular Hypothalamic Nucleus; Peptides; Rats; Rats, Wistar; Sodium Chloride; Supraoptic Nucleus; Tyrosine 3-Monooxygenase

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

Immunoreactive-vasopressin, -oxytocin, -dynorphin, -dynorphin-(1-8), -alpha-neo-endorphin and -[Met]enkephalin were, in each case, present in greater concentrations in dorsal as compared to ventral, and lumbo-sacral as compared to cervico-thoracic, spinal cord. These differences were significantly more pronounced for vasopressin and oxytocin than for the other peptides. Lesions of the hypothalamic paraventricular nucleus depleted levels of immunoreactive-vasopressin and -oxytocin throughout the cord whereas levels of the opioid peptides therein were unaffected. In contrast, destruction of either the supraoptic or suprachiasmatic nucleus failed to change the content of immunoreactive-vasopressin, -oxytocin or any of the opioid peptides in the cord. Dehydration for 3 days depressed levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate lobe of the pituitary. In distinction, the levels of these were not modified in the spinal cord. Further, treatment with the synthetic corticosteroid, dexamethasone, elevated levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate pituitary whereas these were unaffected in the spinal cord. It is concluded that vasopressin and oxytocin in the spinal cord are predominantly derived from the paraventricular nucleus, localized in dorsal lumbo-sacral regions of the cord and insensitive to endocrinological manipulations. These pools may, thus, be modulated differently from their counterparts in the neurohypophysis and have a differing role, possibly in the control of the primary processing, autonomic or motor junctions. Further, there is no evidence from these or our prior studies for a close interrelationship of spinal cord vasopressin with dynorphin-related peptides (or oxytocin with [Met]enkephalin), likewise in contrast to the neurohypophysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Mapping; Dehydration; Dexamethasone; Dynorphins; Endorphins; Enkephalin, Methionine; Hypothalamus; Oxytocin; Rats; Spinal Cord; Vasopressins

The levels of dynorphin-(1-13), leucine enkephalin, beta-endorphin and vasopressin immunoreactivity (ir-DYN, ir-1-ENK, ir-beta-END, ir-VP) have been determined in the anterior and in the neurointermediate lobes of the pituitary of rats subjected to a variety of manipulations. Dehydration of rats by 5 days enforced inhibition of a 2% solution of NaCl resulted in a significant decrease in the levels of ir-DYN, ir-1-ENK and ir-VP, but not in those of ir-beta-END in the neurointermediate lobe of the pituitary. In contrast, substitution of drinking water by a solution containing 20 microgram/ml dexamethasone for 5 days produced a significant increase in the neurointermediate pituitary content of ir-DYN, ir-1-ENK and ir-VP, whereas levels of ir-beta-END remained unaffected. This treatment, however, resulted in a significant fall in the ir-beta-END content of the adenopituitary without changing levels of ir-DYN in this structure. Adrenalectomy was associated with a significant decrease in the ir-DYN, ir-VP and ir-1-ENK content of the neurointermediate lobe of the pituitary and a pronounced elevation in the ir-beta-END but not ir-DYN content of the adenohypophysis. These observations are indicative that the regulation mechanisms of the functional state of particular endorphins differ between the anterior and neurointermediate lobes of the pituitary. The concomitant alterations in levels of ir-DYN, ir-1-ENK and ir-VP detected suggest that a common or similar mechanism of regulation may exist for these peptides. A common biosynthetic origin, however, appears to be unlikely, since Brattleboro rats which are unable to synthesize vasopressin possess unchanged ir-DYN- and ir-1-ENK- levels in the pituitary.

Topics: Adrenalectomy; Animals; beta-Endorphin; Dehydration; Dexamethasone; Diabetes Insipidus; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalins; Male; Peptide Fragments; Pituitary Gland; Rats; Rats, Inbred Strains; Sodium Chloride; Vasopressins

Topics: Animals; Dehydration; Drinking; Dynorphins; Endorphins; Male; Pituitary Gland, Posterior; Rats; Sodium Chloride; Vasopressins