Molecular cloning of the receptor for human antidiuretic hormone

Birnbaumer, Mariel; Seibold, Anita; Gilbert, S.; Ishido, Masami; Barberis, Claude; Antaramián, Anaid; Brabet, Philippe; Rosenthal, Walter

doi:10.1038/357333a0

Cited by 504 publications

(279 citation statements)

References 17 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…The hereditary (congenital) form of NDI is relatively rare, and is known to be caused by mutations in two genes, the arginine vasopressin type 2 receptor (AVPR2) and the water channel aquaporin 2 (AQP2) [1][2][3][4]. These two genes encode two membrane proteins that are oppositely located at the basolateral and apical membranes of the collecting duct principal cells, respectively, and constitute the fundamental components of urine concentrating machinery [5,6].…”

Section: Introductionmentioning

confidence: 99%

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

et al. 2012

View full text Add to dashboard Cite

Background Familial form of nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90 % of NDI families carry disease-causing mutations in AVPR2 and 10 % carry the mutations in AQP2; however, these percentages have not been supported by actual data. It is also unknown whether these percentages vary in different ethnic groups. Methods Gene mutation analyses were performed for 78 Japanese NDI families. All exons and intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced. Results A total of 62 families (79 %) carried diseasecausing mutations in AVPR2, while nine families (12 %) carried mutations in AQP2. We identified 22 novel putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding AVPR2, 52 disease-causing mutations were identified. Among them, missense mutations were most common (54 %), followed by deletion mutations. In the 64 women who had monoallelic disease-causing AVPR2 mutations, 16 (25 %) had NDI symptoms, including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations were identified in nine families. Two missense mutations and one deletion mutation showed a recessive inheritance, while one missense mutation and five small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance.Conclusions Most Japanese NDI families carry diseasecausing mutations in AVPR2 and 12 % carry mutations in AQP2. A total of 22 novel putatively disease-causing mutations were identified. The relatively high occurrence of symptomatic carriers of AVPR2 mutations needs attention.

show abstract

Section: Introductionmentioning

confidence: 99%

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

et al. 2012

View full text Add to dashboard Cite

show abstract

“…These results indicate that the 46-kDa species do not contain the NH 2 -terminal portion of the receptor. The experimental data reported so far indicate that photolabeled V1a receptors on membranes from transfected CHO cells are cleaved by proteases present in the membrane preparation and that proteolytic cleavage occurs in the NH 2 peptide-binding domains covalently-bound to the photoactivatable linear antagonist, photolabeled receptors were electroeluted from a preparative SDS-PAGE and then subjected to enzymatic cleavage by endoproteinases. Lys-C protease and V8 protease (Glu-C) were used either alone or in combination.…”

Section: Binding and Coupling Properties Of The Wild-type Receptor-mentioning

confidence: 99%

“…V1a, V1b, and oxytocin receptors activate phospholipase C, resulting in the production of inositol 1,4,5-trisphosphate and diacylglycerol, mobilization of intracellular calcium and activation of protein kinase C. V2 receptors stimulate adenylyl cyclase, resulting in the accumulation of cyclic AMP and activation of protein kinase A. All receptor subtypes from several mammalian species have been recently cloned (2)(3)(4)(5), as well as closely related receptors from bony fishes and invertebrates (6,7).…”

mentioning

confidence: 99%

Mapping Peptide-binding Domains of the Human V1a Vasopressin Receptor with a Photoactivatable Linear Peptide Antagonist

Phalipou

Cotte

Carnazzi

et al. 1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The study of antagonist-binding domains of the human V1a vasopressin receptor was performed using a radioiodinated photoreactive peptide antagonist. This ligand displayed a high affinity for the receptor expressed in Chinese hamster ovary cell membranes, and specifically labeled two protein bands with apparent molecular mass at 85-90 and 46 kDa. Our results clearly show that the V1a receptor is degraded during incubation with the ligand and that the 46-kDa species is probably the result of the 85-90-kDa species proteolytic cleavage. Truncation of the receptor was then confirmed by deglycosylation with N-glycosidase F. A monoclonal antibody directed against a c-Myc epitope added at the receptor NH 2 terminus allowed immunoprecipitation of the 85-90-kDa photolabeled species. The 46-kDa photolabeled protein never immunoprecipitated, indicating that the truncated form of the receptor lacks the NH 2 terminus region. To localize photolabeled domains of the receptor, the 46-kDa protein was cleaved with V8 and/or Lys-C endoproteinases. The identity of the smallest photolabeled fragment, observed at approximately 6 kDa, was then confirmed by mutation of the potential V8 cleavage sites. Our results indicate that covalent labeling of the vasopressin V1a receptor with the photoreactive antagonist occurs in a region including transmembrane domain VII (residues Asn 327 -Lys 370 ).Neurohypophysial hormones, arginine-vasopressin (AVP) 1 and oxytocin, exert a wide range of physiological effects through binding to specific membrane receptors belonging to the G protein-coupled receptor (GPCR) superfamily. To date, three AVP receptor subtypes and one oxytocin receptor have been pharmacologically and functionally described (1). V1a, V1b, and oxytocin receptors activate phospholipase C, resulting in the production of inositol 1,4,5-trisphosphate and diacylglycerol, mobilization of intracellular calcium and activation of protein kinase C. V2 receptors stimulate adenylyl cyclase, resulting in the accumulation of cyclic AMP and activation of protein kinase A. All receptor subtypes from several mammalian species have been recently cloned (2-5), as well as closely related receptors from bony fishes and invertebrates (6, 7).Analysis of the primary sequence of these receptors suggests that they possess the same general architecture with seven transmembrane helices as other well characterized G proteincoupled receptors. Moreover, the comparison of their amino acid sequence reveals significant homology within the putative transmembrane regions (TM) and within the first and second extracellular loops as well. The natural ligands for the receptors of the AVP/oxytocin family are also closely structurally related. All are nonapeptides composed of a 6-amino acid disulfide-linked ring and a COOH terminus tripeptide.Peptides of the AVP/oxytocin series were subjected to an extensive analysis of structure-activity relationships. These studies (for review, see Refs. 8 -11) led to the production of a profusion of valuable pharmacological probes for asse...

show abstract

“…7 The expression and activity of AQP2 are regulated by the antidiuretic hormone (vasopressin, AVP) via the G-protein coupled AVP-2 receptor (V2R). 8 The binding of AVP to the V2R leads to the activation of the G-protein Gs, followed by activation of adenylate cyclase (AC), increased cyclic adenosine monophosphate (cAMP) levels, activation of protein kinase A (PKA), and finally phosphorylation of AQP2 9 and translocation to the …”

mentioning

confidence: 99%

Acute Rejection Modulates Gene Expression in the Collecting Duct

Edemir

Reuter²,

Borgulya³

et al. 2008

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Kidney transplantation, especially when associated with acute rejection, leads to changes in the expression of many genes, including those encoding solute transporters and water channels. In a rat model of acute rejection after allogeneic renal transplantation, impaired renal function, increased urine volume, and increased fractional excretion of sodium were observed. Gene array analysis revealed that these findings were associated with significant downregulation of water channels (aquaporin-1, -2, -3, and -4) and transporters of sodium, glucose, urea, and other solutes. In addition, changes in expression of various receptors, kinases, and phosphatases that modulate the expression or activity of renal transport systems were observed. Syngeneic transplantation or treatment with cyclosporine A following allogeneic transplantation did not impair graft function but did lead to the downregulation of aquaporin-1, -3, and -4 and several solute transporters. However, expression of aquaporin-2 and the epithelial sodium channel did not change, suggesting that the downregulation of these transporters following allogeneic transplantation is rejection-dependent. In conclusion, changes in gene expression may explain the impaired handling of solute and water after allogeneic transplantation, especially during acute rejection. Treatment with cyclosporine A improves the regulation of solute and water by preventing the downregulation of aquaporin-2 and epithelial sodium channel, even though many other transporter genes remain downregulated. Renal transplantation (TX) in humans is often accompanied by increased transport capacities of the graft and disturbances in salt and water homeostasis. 1-3 Half-life of grafts with normal function after TX is 11.5 yr compared with 7.2 yr for those with impaired renal function. 4 A better understanding of the underlying cellular and molecular mechanisms leading to such changes may help to increase longterm graft survival.Previously, using an allogeneic rat renal TX (aTX) model, we have demonstrated acute changes in expression and function of several transporters and receptors after aTX. 5,6 For example, the expression of Na ϩ /H ϩ -exchanger-3 (NHE3), aquaporin-2 (AQP2), and the epithelial Na ϩ channel (ENaC) were downregulated at the protein and mRNA level. Major transporters for water and Na ϩ reabsorption in the collecting duct (CD) are ENaC and AQP2. 7 The expression and activity of AQP2 are regulated by the antidiuretic hormone (vasopressin, AVP) via the G-protein coupled AVP-2 receptor (V2R). 8 The binding of AVP to the V2R leads to the activation of the G-protein Gs, followed by activation of adenylate cyclase (AC), increased cyclic adenosine monophosphate (cAMP) levels, activation of protein kinase A (PKA), and finally phosphorylation of AQP2 9 and translocation to the

show abstract

Molecular cloning of the receptor for human antidiuretic hormone

Cited by 504 publications

References 17 publications

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

Mapping Peptide-binding Domains of the Human V1a Vasopressin Receptor with a Photoactivatable Linear Peptide Antagonist

Acute Rejection Modulates Gene Expression in the Collecting Duct

Contact Info

Product

Resources

About