Functional Characterization of V2-Vasopressin Receptor Substitutions (R137H/C/L) Leading to Nephrogenic Diabetes Insipidus and Nephrogenic Syndrome of Inappropriate Antidiuresis; Implications for treatments
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چکیده
Moulay D. Rochdi, Gabriel A. Vargas, Eric Carpentier, Geneviève Oligny-Longpré, Stanford Chen, Abraham Kovoor, Stephen E. Gitelman, Stephen M. Rosenthal, Mark von Zastrow and Michel Bouvier* Institut de Recherche en Immunologie et Cancérologie, Département de Biochimie and Groupe de Recherche Universitaire sur le Médicament, Université de Montréal, Montréal, Québec, H3C 3J7, Canada (M.D.R., E.C., G.O.-L., M.B.); Department of Psychiatry (G.A.V., S.C., A.K., M.vZ), Department Cellular & Molecular Pharmacology (M.vZ), and Department of Pediatrics, Division of Endocrinology (S.E.G., S.M.R.), UCSF, San Francisco, CA, USA Molecular Pharmacology Fast Forward. Published on February 16, 2010 as doi:10.1124/mol.109.061804
منابع مشابه
Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments.
Substitution of arginine-137 of the vasopressin type 2 receptor (V2R) for histidine (R137H-V2R) leads to nephrogenic diabetes insipidus (NDI), whereas substitution of the same residue to cysteine or leucine (R137C/L-V2R) causes the nephrogenic syndrome of inappropriate antidiuresis (NSIAD). These two diseases have opposite clinical outcomes. Still, the three mutant receptors were shown to share...
متن کاملNephrogenic Syndrome of Inappropriate Antidiuresis
Mutations in the vasopressin V2 receptor gene are responsible for two human tubular disorders: X-linked congenital nephrogenic diabetes insipidus, due to a loss of function of the mutant V2 receptor, and the nephrogenic syndrome of inappropriate antidiuresis, due to a constitutive activation of the mutant V2 receptor. This latter recently described disease may be diagnosed from infancy to adult...
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Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-funct...
متن کاملA novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.
Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation...
متن کاملFunctional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level.
The protein product of the AVPR2 gene, coding for the arginine vasopressin receptor type 2, is essential for vasopressin-dependent concentration of the urine. The arginine residue at position 137 in the protein product of this gene is uniquely pivotal for function. The R137H mutant inactivates the receptor conferring congenital nephrogenic diabetes insipidus, whereas activating mutations at thi...
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