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)

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked recessive disease characterized by insensitivity of the distal nephron to the antidiuretic effect of arginine vasopressin. The hypothesis that the defect underlying NDI might be a dysfunctional renal vasopressin V2 receptor has recently been proven by the identification of mutations in the V2 receptor gene in NDI patients. We examined thirteen unrelated Dutch NDI families and identified thirteen distinct and unique mutations. These included nine missense mutations, two nonsense mutations and two small deletions and were found in the extracellular domains II, III and IV, the intracellular domains II and IV and in the transmembrane loops I, II, IV and V of the vasopressin type 2 receptor. In the families with multiple NDI patients the mutated gene cosegregated with the disease. Our data suggest a higher mutation frequency in male than in female gametes. No discrepancies between carrier detection by means of DNA analysis with closely linked polymorphic markers and the definite diagnosis based on sequencing data were found.
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PMID:Inheritance of mutations in the V2 receptor gene in thirteen families with nephrogenic diabetes insipidus. 793 35

Congenital nephrogenic diabetes insipidus is a rare hereditary disease characterized by a renal insensitivity to circulating vasopressin. Genetic linkage studies have demonstrated that the gene responsible for congenital nephrogenic diabetes insipidus is located in region 28 of the X chromosome long arm. That the gene coding for the vasopressin V2 receptor is also located in the q28-qter of chromosome X suggests that the signalisation defect in congenital nephrogenic diabetes insipidus is at the level of the receptor itself. Indeed, congenital nephrogenic diabetes insipidus is a genetically heterogeneous disease since several point mutations in the vasopressin V2 receptor gene nucleotide sequence have been observed in different families of afflicted patients. Moreover, the observation that one of these mutations leads to a lack of cyclic AMP production in response to vasopressin confirms that mutations of the vasopressin V2 receptor sequence are the molecular defects responsible for congenital nephrogenic diabetes insipidus.
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PMID:[Congenital nephrogenic diabetes insipidus]. 793 38

Nephrogenic diabetes insipidus (NDI) presents a rarely encountered but challenging fluid management problem in the perioperative period. This case is that of a patient with a perforated duodenal ulcer and previously undiagnosed NDI who received standard preoperative and postoperative hydration with normal saline, causing hypernatremia and an inappropriate diuresis. The resulting hypernatremia and hyperosmolality required aggressive hypotonic fluid replacement to return to preoperative values. Though refractory to 1-desamino-8-D-argenine-vasopressin (dDAVP), thiazide diuretics and nonsteroidal anti-inflammatory agents have a role in managing selected patients. Early diagnosis with careful fluid and electrolyte management are critical in successful management of these patients in the perioperative period.
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PMID:Nephrogenic diabetes insipidus secondary to lithium therapy in the postoperative patient: a case report. 797 76

The mutation of the type-2 vasopressin receptor (V2R) apparently responsible for X-linked congenital nephrogenic diabetes insipidus (CNDI) in the Q3 family consists of a T to C transition in codon 113, causing the change of Arg-113 to Trp. Arg-113 is located in the putative first extracellular loop of the V2R next to a frequently conserved Cys thought to interact via a disulfide bridge with a Cys of the second extracellular loop. The present study explored whether this mutation may account for the CNDI phenotype. The mutation was excised from the genomic DNA of a Q3 patient and introduced into the V2R cDNA, which was then placed into an expression plasmid and transfected into COS cells for transient expression and murine L cells for stable expression. Studies with L cells expressing similar levels of wild type and Q3 receptors showed that the mutant receptor has a 20-fold reduced affinity for arginine vasopressin (AVP) and stimulates adenylyl cyclase with an EC50 that is increased by a factor of about 60-fold. The same shift in the EC50 for adenylyl cyclase stimulation was obtained when deamino[8-D-Arg]vasopressin was substituted for AVP. Studies with COS cells revealed that at equal levels of transfected DNA, the mutant receptor is expressed at lower levels (about 20%) than the wild type receptor, indicating that the mutation hinders the transport of the receptor to the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system. 798 50

Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A-->G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin.
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PMID:Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus. 804 48

Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly transmitted in an X chromosome-linked recessive manner and characterized by the lack of renal response to the action of antidiuretic hormone [Arg8]vasopressin. The vasopressin type 2 receptor (V2R) has been suggested to be the gene that causes the disease, and its role in disease pathogenesis is supported by mutations within this gene in affected individuals. Using the PCR, denaturing gradient gel electrophoresis, and direct DNA sequencing, we examined the V2R gene in four unrelated kindreds. In addition, linkage analysis with chromosome Xq28 markers was done in one large Brazilian kindred with an apparent unusual X chromosome-linked dominant inheritance pattern. In one family, a mutation in codon 280, causing a Tyr-->Cys substitution in the sixth transmembrane domain of the receptor, was found. In the other three additional families with nephrogenic diabetes insipidus, the V2R-coding region was normal in sequence. In one large Brazilian kindred displaying an unusual X chromosome-linked dominant mode of inheritance, the disease-related gene was localized to the same region of the X chromosome as the V2R, but no mutations were found, thus raising the possibility that this disease is caused by a gene other than V2R.
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PMID:Nephrogenic diabetes insipidus: an X chromosome-linked dominant inheritance pattern with a vasopressin type 2 receptor gene that is structurally normal. 807 3

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene.
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PMID:X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis. 810 96

Concentration of urine in mammals is regulated by the antidiuretic hormone vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of water channels in apical membranes of principal cells in collecting ducts. In nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to vasopressin. A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, aquaporin-2 is essential for vasopressin-dependent concentration of urine.
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PMID:Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. 814 Apr 21

In healthy subjects, intravenous infusion of the selective V2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal, indicating the absence of a V1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V2-receptor stimulation.
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PMID:1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus. 823 94

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of arginine vasopressin. The disease gene has been assigned to the subtelomeric region of the X chromosome long arm by demonstrating close linkage between NDI and several X-chromosomal DNA markers. The finding of closely linked genetic markers is useful in the diagnosis of NDI. Receptor studies in patients have indicated that NDI might be due to the absence or an abnormality of the adenylate cyclase-bound vasopressin type 2 receptor. This assumption was supported by the discovery of functional vasopressin V2 receptor activity in somatic cell hybrid cell lines that carried at least the distal part of the human X chromosome long arm. Definite evidence for a V2 receptor defect being the cause of NDI was found in a recent study demonstrating point mutations in the V2 receptor gene from affected individuals. Direct mutation analysis is now applicable for accurate carrier detection and early (prenatal) diagnosis.
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PMID:Nephrogenic diabetes insipidus: identification of the genetic defect. 825 44


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