title: Relief of nocturnal enuresis by desmopressin is kidney and vasopressin type 2 receptor independent.
abstract: Primary nocturnal enuresis (PNE) is a common problem in childhood and adolescence. Although various treatments are highly effective, a common underlying hypothesis on the pathogenesis is lacking. The success of desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, has been attributed to increased renal water reabsorption that is mediated by activation of the renal vasopressin V2 receptor (V2R). However, this effect does not explain other symptoms of PNE, such as the failure to arouse upon bladder distension. This study identified a family in which one child displayed PNE and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). Cell-biologic investigations revealed that V2R-C358X is retained in the endoplasmic reticulum and is unstable, which explains his nephrogenic diabetes insipidus. Consistently, extrarenal V2R-mediated responses were absent in the patient who was treated with desmopressin. Administration of desmopressin, however, changed his PNE into nocturia, because he now still voided unchanged high urinary volumes at night but woke up and went to the bathroom. Withdrawal of desmopressin was accompanied by bedwetting, whereas reintroduction again relieved the symptoms. Therefore, these data indicate that neither a functioning renal concentration system nor a functional V2R is needed for the therapeutic benefit of desmopressin in PNE. Rather, it suggests that another vasopressin receptor and other organ(s) is the target for desmopressin to relieve PNE.
authors: Department of Physiology, Nijmegen Centre of Molecular Life Sciences, Nijmegen, Netherlands.
authors: Joris H
authors: JH
authors: Robben
authors: Mozes
authors: M
authors: Sze
authors: Nine V
authors: NV
authors: Knoers
authors: Paul
authors: P
authors: Eggert
authors: Peter
authors: P
authors: Deen
authors: Dominik
authors: D
authors: Müller
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002648:Child; D002522:Chlorocebus aethiops; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use*; D018500:Diabetes Insipidus, Nephrogenic / Q000150:complications; D004285:Dogs; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D020125:Mutation, Missense; D053206:Nocturnal Enuresis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D017483:Receptors, Vasopressin / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D017483:Receptors, Vasopressin; D003894:Deamino Arginine Vasopressin