Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnocellular neurons of the hypothalamo-neurohypophysial system play a fundamental role in the maintenance of body homeostasis by secreting vasopressin and oxytocin in response to systemic osmotic perturbations. During chronic hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas, during chronic hyposmolality, these mRNA levels decrease to 10-20% of that of normoosmolar control animals. To determine what other genes respond to these osmotic perturbations, we have analyzed gene expression during chronic hyper- versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially screening cDNA libraries that were generated from supraoptic nucleus tissue punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs by in situ hybridization histochemistry confirmed that they are osmotically regulated. These cDNAs represent a variety of functional classes and include cytochrome oxidase, tubulin, Na(+)-K(+)-ATPase, spectrin, PEP-19, calmodulin, GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins. This analysis therefore suggests that adaptation to chronic osmotic stress results in global changes in gene expression in the magnocellular neurons of the supraoptic nucleus.
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PMID:Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality. 1100 89

The signal transduction mechanisms that mediate osmotic regulation of Na(+)/H(+) exchange are not understood. Recently we demonstrated that hyposmolality increases HCO(3)(-) absorption in the renal medullary thick ascending limb (MTAL) through stimulation of the apical membrane Na(+)/H(+) exchanger NHE3. To investigate the mechanism of this stimulation, MTALs from rats were isolated and perfused in vitro with 25 mM HCO(3)(-)-containing solutions. The phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin (100 nM) and LY-294002 (20 microM) blocked completely the stimulation of HCO(3)(-) absorption by hyposmolality. In tissue strips dissected from the inner stripe of the outer medulla, the region of the kidney highly enriched in MTALs, hyposmolality increased PI 3-K activity 2. 2-fold. Wortmannin blocked the hyposmolality-induced PI 3-K activation. Further studies examined the interaction between hyposmolality and vasopressin, which inhibits HCO(3)(-) absorption in the MTAL via cAMP and often is involved in the development of plasma hyposmolality in clinical disorders. Pretreatment with arginine vasopressin, forskolin, or 8-bromo-cAMP abolished hyposmotic stimulation of HCO(3)(-) absorption, due to an effect of cAMP to inhibit hyposmolality- induced activation of PI 3-K. In contrast to their effects to block stimulation by hyposmolality, PI 3-K inhibitors and vasopressin have no effect on inhibition of apical Na(+)/H(+) exchange (NHE3) and HCO(3)(-) absorption by hyperosmolality. These results indicate that hyposmolality increases NHE3 activity and HCO(3)(-) absorption in the MTAL through activation of a PI 3-K-dependent pathway that is inhibited by vasopressin and cAMP. Hyposmotic stimulation and hyperosmotic inhibition of NHE3 are mediated through different signal transduction mechanisms.
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PMID:Hyposmolality stimulates Na(+)/H(+) exchange and HCO(3)(-) absorption in thick ascending limb via PI 3-kinase. 1102 92

Because the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can cause neurologic sequelae with the potential to affect long-term outcomes, its prompt recognition and treatment are essential. Normally, antidiuretic hormone (ADH) is secreted when effective circulating blood volume is decreased. SIADH is marked by secretion of ADH in the presence of effective or normal circulating blood volume. This causes plasma hyponatremia simultaneously with plasma hypo-osmolality and inappropriate hyperosmolality of the urine. This article explains the pathophysiology of the syndrome; describes its diagnosis, clinical course, and treatment; and exemplifies the syndrome with a case study.
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PMID:SIADH: a case review. 1214 36

The vasopressin (VP) magnocellular neurosecretory cells (MNCs) in the supraoptic and paraventricular (PVN) nuclei are regulated by estrogen and exhibit robust expression of estrogen receptor (ER)-beta. In contrast, only approximately 7.5% of oxytocin (OT) MNCs express ER-beta. We examined the osmotic regulation of ER-beta mRNA expression in MNCs using quantitative in situ hybridization histochemistry. Hyper-osmolality induced via 2% hypertonic saline ingestion significantly decreased, whereas sustained hypo-osmolality induced via d-d-arginine VP and liquid diet increased ER-beta mRNA expression in MNCs (p < 0.05). Thus, the expression of ER-beta mRNA correlated inversely with changes in plasma osmolality. Because hyper-osmolality is a potent stimulus for VP and OT release, this suggests an inhibitory role for ER-beta in MNCs. Immunocytochemistry demonstrated that the decrease in ER-beta mRNA was translated into depletion of receptor protein content in hyper-osmotic animals. Numerous MNCs were positive for ER-beta in control animals, but they were virtually devoid of ER-beta-immunoreactivity (IR) in hyper-osmotic animals. The osmotically induced decrease in ER-beta expression was selective for MNCs because ER-beta-IR remained unaltered in PVN parvocellular neurons. Plasma estradiol and testosterone were not correlated with ER-beta mRNA expression after osmotic manipulation, suggesting that ER-beta expression was not driven by ligand availability. Expression of FOS-IR in MNCs with attenuated ER-beta-IR, and the absence of FOS-IR in parvocellular neurons that retain ER-beta-IR suggest a role for neuronal activation in the regulation of ER-beta expression in MNCs. Thus, osmotic modulation of ER-beta expression in MNCs may augment or attenuate an inhibitory effect of gonadal steroids on VP release.
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PMID:Osmotic regulation of estrogen receptor-beta in rat vasopressin and oxytocin neurons. 1276 14

Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behoves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Because body water is the primary determinant of the osmolality of the extracellular fluid, disorders of body water homeostasis can be divided into hypo-osmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classical hyperosmolar disorder is diabetes insipidus (DI), and the classical hypo-osmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This chapter first reviews the regulatory mechanisms underlying water and sodium metabolism, the two major determinants of body fluid homeostasis. The major disorders of water metabolism causing hyperosmolality and hypo-osmolality, DI and SIADH, are then discussed in detail, including the pathogenesis, differential diagnosis and treatment of these disorders.
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PMID:Disorders of body water homeostasis. 1468 85

The robust expression of oestrogen receptor beta (ER-beta) in magnocellular vasopressin neurones has focused attention on the role of this receptor and the gonadal steroids in the regulation of vasopressin secretion. Although the effects of gonadal steroids on vasopressin secretion have been the subject of many studies, there is no consensus in the literature as to their role. Possible reasons for the diverse findings are discussed, including diversity in the types, site and level of expression of steroid receptors across species, gender and physiological conditions. The physiological regulation of expression is of particular interest because ER-beta mRNA expression in vasopressin neurones is inversely correlated to the osmotic state of the animal. Chronic hyperosmolality inhibits ER-beta mRNA expression in magnocellular vasopressin neurones, while chronic hypo-osmolality enhances expression. This is consistent with an inhibitory role for ER-beta because hyperosmolality is a potent stimulus for vasopressin secretion, whereas vasopressin secretion is maximally inhibited by chronic hypo-osmolality. An inhibitory role is also indicated by in vitro experiments demonstrating inhibition of osmotically stimulated vasopressin secretion by oestrogen and testosterone, and ER-beta mediated inhibition of NMDA-stimulated vasopressin secretion. The challenge remains to elucidate the mechanism of this inhibition, and to understand its significance for maintenance of whole-body fluid and electrolyte homeostasis.
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PMID:Oestrogen receptor beta: role in neurohypophyseal neurones. 1508 76

In the medullary thick ascending limb (MTAL) of rat kidney, inhibiting basolateral Na(+)/H(+) exchange with either amiloride or nerve growth factor (NGF) results secondarily in inhibition of apical Na(+)/H(+) exchange, thereby decreasing transepithelial HCO(3)(-) absorption. To assess the possible role of the Na(+)/H(+) exchanger NHE1 in this regulatory process, MTALs from wild-type and NHE1 knockout (NHE1(-/-)) mice were studied using in vitro microperfusion. The rate of HCO(3)(-) absorption was decreased 60% in NHE1(-/-) MTALs (15.4 +/- 0.5 pmol.min(-1).mm(-1) wild-type vs. 6.0 +/- 0.5 pmol.min(-1).mm(-1) NHE1(-/-)). Transepithelial voltage, an index of the NaCl absorption rate, did not differ in wild-type and NHE1(-/-) MTALs. Basolateral addition of 10 microM amiloride or 0.7 nM NGF decreased HCO(3)(-) absorption by 45-49% in wild-type MTALs but had no effect on HCO(3)(-) absorption in NHE1(-/-) MTALs. Inhibition of HCO(3)(-) absorption by vasopressin and stimulation by hyposmolality, both of which regulate MTAL HCO(3)(-) absorption through primary effects on apical Na(+)/H(+) exchange, were similar in wild-type and NHE1(-/-) MTALs. Thus the regulatory defect in NHE1(-/-) MTALs is specific for factors (bath amiloride and NGF) shown previously to inhibit HCO(3)(-) absorption through primary effects on basolateral Na(+)/H(+) exchange. These findings demonstrate a novel role for NHE1 in transepithelial HCO(3)(-) absorption in the MTAL, in which basolateral NHE1 controls the activity of apical NHE3. Paradoxically, a reduction in NHE1-mediated H(+) extrusion across the basolateral membrane leads to a decrease in apical Na(+)/H(+) exchange activity that reduces HCO(3)(-) absorption.
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PMID:Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice. 1529 47

Hypoosmolality produces a dramatic inhibition of vasopressin (VP) and oxytocin gene expression in the supraoptic nucleus (SON). This study examines the effect of sustained hypoosmolality on global gene expression in the oxytocin and VP magnocellular neurons of the hypothalamo-neurohypophysial system, to identify genes associated with the magnocellular neuron's adaptation to this physiological condition. Using laser microdissection of the SON, T7-based linear amplification of its RNA, and a 35,319-element cDNA microarray, we compare gene expression profiles between SONs in normoosmolar (control), 1-desamino-[8-D-arginine]-VP-treated normoosmolar, and hypoosmolar rats. We found 4959 genes with statistically significant differences in expression between normosmolar control and the hypoosmolar SONs, with 1564 of these differing in expression by more than 2-fold. These genes serve a wide variety of functions, and most were up-regulated in gene expression in hypoosmolar compared with control SONs. Of these, 90 were preferentially expressed in the SON, and 44 coded for transcription-related factors, of which 15 genes were down-regulated and 29 genes were up-regulated in the hypoosmolar rat SONs. None of these transcription-related factor genes significantly changed in expression after sustained 1-desamino-[8-D-arginine]-VP-treatment alone, indicating that these changes were associated with the hypoosmolar state and not due solely to a decreased activity in the SON. Quantitative in situ hybridization histochemistry was selectively used to confirm and extend these microarray observations. These results indicate that the hypoosmolar state is accompanied by a global, but selective, increase in expression of a wide variety of regulatory genes in the SON.
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PMID:Regulation of gene expression in magnocellular neurons in rat supraoptic nucleus during sustained hypoosmolality. 1559 Nov 43

In the renal medullary thick ascending limb (MTAL), inhibiting the basolateral NHE1 Na(+)/H(+) exchanger with amiloride or nerve growth factor (NGF) results secondarily in inhibition of the apical NHE3 Na(+)/H(+) exchanger, thereby decreasing transepithelial HCO3- absorption. MTALs from rats were studied by in vitro microperfusion to identify the mechanism underlying cross-talk between the two exchangers. The basolateral addition of 10 microM amiloride or 0.7 nM NGF decreased HCO3- absorption by 27-32%. Jasplakinolide, which stabilizes F-actin, or latrunculin B, which disrupts F-actin, decreased basal HCO3- absorption by 30% and prevented the inhibition by amiloride or NGF. Jasplakinolide had no effect on HCO3- absorption in tubules bathed with amiloride or a Na(+)-free bath to inhibit NHE1. Jasplakinolide and latrunculin B did not prevent inhibition of HCO3- absorption by vasopressin or stimulation by hyposmolality, factors that regulate HCO3- absorption through primary effects on apical Na(+)/H(+) exchange. Treatment of MTALs with amiloride or NGF for 15 min decreased polymerized actin with no change in total cell actin, as assessed both by fluorescence microscopy and by actin Triton X-100 solubility. Jasplakinolide prevented amiloride-induced actin remodeling. Vasopressin, which inhibits HCO3- absorption by an amount similar to that observed with amiloride and NGF but does not act via NHE1, did not affect cellular F-actin content. These results indicate that basolateral NHE1 regulates apical NHE3 and HCO3- absorption in the MTAL by controlling the organization of the actin cytoskeleton.
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PMID:The basolateral NHE1 Na+/H+ exchanger regulates transepithelial HCO3- absorption through actin cytoskeleton remodeling in renal thick ascending limb. 1564 22

The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V(2) vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.
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PMID:Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism. 1591 74


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