preproenkephalin and Dehydration

Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine kappa-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine kappa-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 +/- 0.5 to 9.0 +/- 0.6 spikes s(1)) and phasic activity (from 4.2 +/- 0.7 to 7.8 +/- 0.9 spikes s(1)), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective -opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 +/- 0.8 to 5.3 +/- 0.6 spikes s(1)) and dehydrated rats (from 6.4 +/- 0.5 to 9.1 +/- 1.2 spikes s(1)), indicating that kappa-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation.

Topics: Action Potentials; Animals; Cholecystokinin; Dehydration; Electrophysiology; Enkephalins; Female; Hypernatremia; Hyponatremia; Immunohistochemistry; In Situ Hybridization; Naltrexone; Narcotic Antagonists; Neurons; Oxytocin; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; RNA, Messenger; Vasopressins

Changes in neuropeptide gene expression in the hypothalami of sheep subjected to psychological stress (isolation, 1 h; n = 3) or dehydration (48 h; n = 3) were examined using in-situ hybridization histochemistry. Compared with non-stressed euhydrated control animals (n = 3), isolation induced significant accumulation of mRNA for corticotrophin-releasing hormone, pro-enkephalin and pro-dynorphin (DYN) in the paraventricular nucleus (PVN), but no change in mRNA content within the supraoptic nucleus (SON). By contrast, dehydration significantly increased DYN mRNA in the magnocellular neurones of the PVN and SON. However, neither isolation nor dehydration altered the expression of mRNA for vasopressin (AVP) in either the PVN or the SON. These results indicate that in the ovine hypothalamus (1) stress represents a powerful stimulus to co-ordinated neuropeptide synthesis and (2) expression of DYN mRNA and AVP mRNA may be independently regulated during changes in plasma osmolality.

Topics: Animals; Arginine Vasopressin; Corticotropin-Releasing Hormone; Dehydration; Enkephalins; Gene Expression Regulation; Male; Paraventricular Hypothalamic Nucleus; Protein Precursors; Sheep; Sheep Diseases; Social Isolation; Stress, Physiological; Supraoptic Nucleus

To elucidate the role of leumorphin, a kappa-agonist derived from proenkephalin-B (neoendorphin/dynorphin precursor), in the control of arginine vasopressin (AVP) secretion, we examined the effects of intracerebroventricular (icv) administration of leumorphin on AVP secretion under basal and stimulated conditions in conscious unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal AVP secretion. In 72-h water-deprived rats, icv injection of leumorphin (60 or 600 pmol) also suppressed AVP secretion in a dose-dependent manner. The AVP response induced by icv injection of angiotensin II (100 pmol) was significantly decreased by the simultaneous icv injection of leumorphin (6-600 pmol) in a dose-dependent manner. Intracerebroventricular administration of leumorphin (600 pmol) also reduced the AVP secretion stimulated by icv injection of carbachol (50 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg BW) diminished the inhibitory action of leumorphin (60 pmol) on AVP secretion. However, no effect on AVP secretion was observed after iv injection of leumorphin (600 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on AVP secretion, suggesting its important role in the regulation of AVP secretion in the brain.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Brain; Carbachol; Dehydration; Enkephalins; Injections, Intraventricular; Male; Naloxone; Protein Precursors; Rats; Rats, Inbred Strains

The effects of intracerebroventricular (i.c.v.) injection of leumorphin on the vasopressin secretion induced by angiotensin II or dehydration were studied in conscious unrestrained rats. The vasopressin secretion induced by angiotensin II (100 pmol) was significantly inhibited by the simultaneous injection of leumorphin (6 pmol-600 pmol) in a dose-dependent manner. In 72-hour water-deprived rats, the i.c.v. injection of leumorphin (60 pmol or 600 pmol) significantly suppressed the vasopressin secretion dose-dependently. These results suggest that leumorphin is involved in the regulation of the vasopressin secretion.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Cerebral Ventricles; Dehydration; Enkephalins; Injections, Intraventricular; Male; Protein Precursors; Rats; Rats, Inbred Strains

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