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)

The central and peripheral mechanisms regulate body water balance near an ideal set point. Osmosensitive neurons in the organum vasculosum lamina terminalis (OVLT) in the anterior hypothalamus play a key role in regulating vasopressin release and drinking behaviour. Patients with OVLT lesions are known to have osmostat fluctuations. Although the brain water channel is suggested to participate in osmoreception, the precise molecular mechanisms of osmoreception and thirst appreciation remain to be clarified. Vasopressin gene mutation is responsible for hereditary central diabetes insipidus. Mutant vasopressin precursors have been reported to impair the secretion of wild-type proteins or cause cellular toxicity. Despite the intact production and secretion of vasopressin, the kidney is unable to concentrate urine in nephrogenic diabetes insipidus (NDI). Most congenital NDI patients have mutations in the G protein-coupled vasopressin V2 receptor gene. V2 receptor mutants are shown not to reach the plasma membrane, not to bind AVP, and not to trigger an intracellular cyclic adenosine-monophosphate signal. Congenital NDI with an autosomal recessive inheritance has mutations of Aquaporin-2 gene, a vasopressin-sensitive water channel in the renal inner medullary collecting duct (IMCD). Aquaporin-2 mutant proteins cannot be expressed at the luminal membrane. The corticopapillary osmotic gradient is necessary for renal sensitivity to vasopressin. The vasopressin-regulated urea transporter in IMCD and the chloride channel (CLC-K1) in the ascending loop of the Henle contribute to the formation of the osmotic gradient. NDI has been shown in mice lacking the CLC-K1. The pathophysiological significance of urea transporter and CLC-K1 has yet to be demonstrated in patients with NDI.
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PMID:[Water metabolism and its disturbances]. 1063 21

To analyze the physiological functions of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Homozygous mutant Clcnk1-/- mice produced approximately 5 times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24-hour water deprivation, Clcnk1-/- mice became severely dehydrated and lethargic. Intraperitoneal injection of the V2 agonist, deamino-Cys(1), D-Arg(8) vasopressin, induced an increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice from approximately 1,000 to approximately 3,000 mosm/kg H(2)O, whereas the increase in Clcnk1-/- mice was only from approximately 600 to approximately 840 mosm/kg H(2)O, indicating nephrogenic diabetes insipidus in Clcnk1-/- mice. These results clearly established that CLC-K1 plays a major role in the urinary-concentrating mechanisms.
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PMID:Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride channel. 1101 33

Cl(-) channels play important roles in the regulation of a variety of functions, including electrical excitability, cell volume regulation, transepithelial transport and acidification of cellular organelles. They are expressed in plasma membranes or reside in intracellular organelles. A large number of Cl(-) channels with different functions have been identified. Some of them are highly expressed in the kidney. They include members of the CLC Cl(-) channel family: ClC-K1 (or ClC-Ka), ClC-K2 (or ClC-Kb) and ClC-5. The identification of mutations responsible for human inherited diseases (Bartter syndrome for ClC-Kb and Dent's disease for ClC-5) and studies on knockout mice models have evidenced the physiological importance of these CLC Cl(-) channels, permitting better understanding on their functions in renal tubule epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel, also expressed in renal tubule epithelial cells, is involved in the transepithelial transport of Cl(-) in the distal nephron. This short review focuses on intrarenal distribution, subcellular localization and function of the ClK(-1), ClC-K2 and ClC-5 Cl(-) channels in renal tubule epithelial cells, and the role of the CFTR Cl(-) channel in chloride fluxes elicited by vasopressin in the distal nephron.
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PMID:Expression and function of CLC and cystic fibrosis transmembrane conductance regulator chloride channels in renal epithelial tubule cells: pathophysiological implications. 1747 25

Our understanding of urinary concentrating and diluting mechanisms at the end of the 20th century was based largely on data from renal micropuncture studies, isolated perfused tubule studies, tissue analysis studies and anatomical studies, combined with mathematical modeling. Despite extensive data, several key questions remained to be answered. With the advent of the 21st century, a new approach, transgenic and knockout mouse technology, is providing critical new information about urinary concentrating processes. The central goal of this review is to summarize findings in transgenic and knockout mice pertinent to our understanding of the urinary concentrating mechanism, focusing chiefly on mice in which expression of specific renal transporters or receptors has been deleted. These include the major renal water channels (aquaporins), urea transporters, ion transporters and channels (NHE3, NKCC2, NCC, ENaC, ROMK, ClC-K1), G protein-coupled receptors (type 2 vasopressin receptor, prostaglandin receptors, endothelin receptors, angiotensin II receptors), and signaling molecules. These studies shed new light on several key questions concerning the urinary concentrating mechanism including: 1) elucidation of the role of water absorption from the descending limb of Henle in countercurrent multiplication, 2) an evaluation of the feasibility of the passive model of Kokko-Rector and Stephenson, 3) explication of the role of inner medullary collecting duct urea transport in water conservation, 4) an evaluation of the role of tubuloglomerular feedback in maintenance of appropriate distal delivery rates for effective regulation of urinary water excretion, and 5) elucidation of the importance of water reabsorption in the connecting tubule versus the collecting duct for maintenance of water balance.
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PMID:Mouse models and the urinary concentrating mechanism in the new millennium. 1792 81