Disease relevance of Avpr2

• Interestingly, female mice heterozygous for the V2R mutation showed normal growth but displayed an XNDI-like phenotype, characterized by reduced urine concentrating ability of the kidney, polyuria, and polydipsia [1].
• The nephrogenic diabetes insipidus symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery in the mutants before the onset of hydronephrosis suggest that the congenital obstructive nephropathy is most likely a result of the polyuria [2].
• AQP2 is restricted to renal collecting ducts and has been linked to congenital nephrogenic diabetes insipidus in humans and to lithium-induced nephrogenic diabetes insipidus and fluid retention from congestive heart failure in rat models [3].
• Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure [4].
• In vitro studies in transfected cells have indicated that chemical chaperones including glycerol (0.5-1.2 M) and trimethylamine oxide (TMAO, 50-100 mM) can correct defective trafficking of some proteins, including deltaF508 CFTR in cystic fibrosis and AQP2 mutants in nephrogenic diabetes insipidus [5].

Psychiatry related information on Avpr2

• Effects of water deprivation and deamino [8-D-arginine] vasopressin on [14C]2-deoxyglucose uptake by the hypothalamo-hypophysial system in mice with hereditary nephrogenic diabetes insipidus [6].

High impact information on Avpr2

• We report here that two families of major histocompatibility complex (MHC) class Ib molecules, the M10 and the M1 families, show restricted expression in V2R-expressing neurons [7].
• In rodents, these receptors are thought to be represented by two large multigene families, comprising the V1r and V2r genes, which encode seven-transmembrane proteins [8].
• Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel [9].
• The vasopressin V2 receptor (VPV2R) antagonist OPC31260 has been effective in two animal models of PKD with pathologies that are probably related [10].
• Seven-transmembrane-domain proteins encoded by the vomeronasal receptor V1r and V2r gene superfamilies, and expressed by vomeronasal sensory neurons, are believed to be pheromone receptors in rodents [11].

Chemical compound and disease context of Avpr2

• Furthermore, these mice exhibited marked hypotonic polyuria, polydipsia, and renal unresponsiveness to an antidiuretic hormone, vasopressin, all of which are characteristics consistent with nephrogenic diabetes insipidus [12].
• Vasopressin and ethanol preference. II. Altered preference in two strains of diabetes insipidus rats and nephrogenic diabetes insipidus mice [13].

Biological context of Avpr2

• Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion [14].
• Specifically, we introduced a nonsense mutation known to cause X-linked nephrogenic diabetes insipidus (XNDI) in humans (Glu242stop) into the mouse genome [1].
• Using a combination of genetic and physical mapping, we have localized the murine V2r locus to within 100 kb of L1Cam on the mouse X chromosome in a region syntenic with human Xq28 [15].
• Based on conserved gene order of mouse and human loci in this region, physical mapping using DNA derived from human lymphoblasts has established that the corresponding human loci V2R and L1CAM are linked within 210 kb [15].
• Here, we show that small peptides that serve as ligands for major histocompatibility complex (MHC) class I molecules function also as sensory stimuli for a subset of vomeronasal sensory neurons located in the basal Gao- and V2R receptor-expressing zone of the vomeronasal epithelium [16].

Anatomical context of Avpr2

• AVP-induced vasopressor responses were abolished in the mutant mice; rather, AVP caused a decrease in BP, which occurred in part through V2 receptor-mediated release of nitric oxide from the vascular endothelium [17].
• The V2 vasopressin receptor (V2R) plays a key role in the maintenance of a normal body water balance [1].
• Forty-eight hours after injection membranes were prepared from the inner medulla of the kidneys, and V2R expression was measured by a radioligand binding assay and Western immunoblotting [18].
• The results showed that the vasopressin V2 receptor antagonist microinjected into the ventral hippocampus did not alter the enhancing effect of vasopressin on retrieval and relearning [19].
• In transfected mammalian cells, many NDI-causing AQP2 mutants are retained in the endoplasmic reticulum [20].

Associations of Avpr2 with chemical compounds

• To determine if CD cAMP, generated from increased AVP-V2Rs, was accelerating the PKD, cystic mice and their normal littermates were treated with OPC31260, a relatively specific AVP-V2R antagonist [21].
• Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin [22].
• However, the underlying mechanism by which lithium causes NDI is poorly understood [23].
• Furthermore, neither AVP nor V2 receptor agonist and antagonist alter cellular cAMP [24].
• Alternatively, PGE2 might have reduced the affinities between ADH-receptor units and a component(s) of the series of processes leading to adenyl cyclase activation [25].

Regulatory relationships of Avpr2

• The overexpression and/or overactivity of the AVP-V2R appears to contribute to the progression of PKD since an AVP-V2R antagonist inhibits cystic renal enlargement in the cpk mouse [21].
• AQP1 and AQP3 are also expressed in the kidney where their deletion in mice produces distinct forms of nephrogenic diabetes insipidus [26].
• Monensin-resistant LLC-PK1 cell mutants are affected in recycling of the adenylate cyclase-stimulating vasopressin V2-receptor [27].

Other interactions of Avpr2

• AVP-V2R, AQP2, and AQP3 mRNA expression normally increase between 7 and 14 days [21].
• Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency [28].
• Aldose reductase-deficient mice develop nephrogenic diabetes insipidus [29].
• We concluded that NDI in Clcnk1-/- mice resulted from an impairment in the generation of inner medullary hypertonicity by a dysfunction of the countercurrent systems [30].
• The present study was an attempt to determine whether the vasopressin V2 receptor antagonist or oxytocin receptor antagonist is as effective as the vasopressin V1 receptor antagonist to block the behavioral effect of vasopressin in the ventral hippocampus [19].

Analytical, diagnostic and therapeutic context of Avpr2

• The V2R product from the UrMm chimera was cleaved by a restriction enzyme known to digest only rat product, suggesting the PCR product was produced predominantly by cells derived from the ureteric bud [31].
• Each mouse (male C57BL/6) received 3.6 nmol (approximately 50 microg) of either the control (nonsilencing) or one of the V2R-targeting siRNAs via intravenous injection [18].
• As a model system, we studied a mutant V2 vasopressin receptor (AVPR2) containing the inactivating E242X nonsense mutation which mimics human X-linked nephrogenic diabetes insipidus (XNDI) when introduced into mice via gene targeting techniques [32].
• The effects of water deprivation and the injection of deamino [8-D-arginine] vasopressin (dDAVP) on the metabolic activity of the hypothalamo-neurohypophysial neurones of mice with inherited nephrogenic diabetes insipidus (DI +/+ Severe) have been investigated by quantitative autoradiography using the [14C]2-deoxyglucose (2-DG) technique [6].
• Sequence analysis indicates substantial homology to mouse V1R and V2R VNO receptor families [33].

References