Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were carried out on the right auricle of the right atrium of two-day-old rats placed in a special chamber perfused with Ringer-Locke solution at room temperature. The contractions rate of the auricle was counted with the use of a stereomicroscope. The following amino acids dissolved in Ringer-Locke solution were tested: glycine, glutamic acid, serine, alanine, aspartic acid, gamma aminobutyric acid, leucine, and peptides: vasopressin and oxytocin. Glutamic acid in a concentration of 10(-1) mol/l induced a decrease in auricle contraction rate by 25%. Alanine in concentration 10(-2) mol/l induced a decrease by 22%. Leucine in concentration 10(-2) mol/l induced a decrease by 16% and in concentration ten times higher a decrease by 28%. The other tested amino acids, vasopressin and oxytocin in concentration used had no influence on the rate of contraction frequency of the isolated auricle.
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PMID:The influence of amino acids, vasopressin and oxytocin on spontaneous contraction of the right auricle of the right atrium of two-day-old rats in vitro. 654 86

We investigated the inhibitory role of the nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway on receptor-activated TRPC6 channels in both a heterologous expression system (HEK293 cells) and A7r5 vascular myocytes. Cationic currents due to TRPC6 expression were strongly suppressed (by approximately 70%) by a NO donor SNAP (100 microm) whether it was applied prior to muscarinic receptor stimulation with carbachol (CCh; 100 microm) or after G-protein activation with intracellular perfusion of GTPgammaS (100 microm). A similar extent of suppression was also observed with a membrane-permeable analogue of cGMP, 8Br-cGMP (100 microm). The inhibitory effects of SNAP and 8Br-cGMP on TRPC6 channel currents were strongly attenuated by the presence of inhibitors for guanylyl cyclase and PKG such as ODQ, KT5823 and DT3. Alanine substitution for the PKG phosphorylation candidate site at T69 but not at other sites (T14A, S28A, T193A, S321A) of TRPC6 similarly attenuated the inhibitory effects of SNAP and 8Br-cGMP. SNAP also significantly reduced single TRPC6 channel activity recorded in the inside-out configuration in a PKG-dependent manner. SNAP-induced PKG activation stimulated the incorporation of (32)P into wild-type and S321A-mutant TRPC6 proteins immunoprecipitated by TRPC6-specific antibody, but this was greatly attenuated in the T69A mutant. SNAP or 8Br-cGMP strongly suppressed TRPC6-like cation currents and membrane depolarization evoked by Arg(8)-vasopressin in A7r5 myocytes. These results strongly suggest that TRPC6 channels can be negatively regulated by the NO-cGMP-PKG pathway, probably via T69 phosphorylation of the N-terminal. This mechanism may be physiologically important in vascular tissues where NO is constantly released from vascular endothelial cells or nitrergic nerves.
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PMID:Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. 1861 65

Almost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the arginine-vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the published mutations/variants in AVPR2. We planned to perform a comprehensive review of all the AVPR2 mutations/variants and to test whether any amino acid change causing a missense mutation is significantly more or less common than others. We performed a Medline search and collected detailed information regarding all AVPR2 mutations and variants. We performed a frequency comparison between mutated and wild-type amino acids and codons. We predicted the mutation effect or reported it based on published in vitro studies. We also reported the ethnicity of each mutation/variant carrier. In summary, we identified 211 AVPR2 mutations which cause NDI in 326 families and 21 variants which do not cause NDI in 71 NDI families. We described 15 different types of mutations including missense, frameshift, inframe deletion, deletion, insertion, nonsense, duplication, splicing and combined mutations. The missense mutations represent the 55.83% of all the NDI published families. Arginine and tyrosine are significantly (P = 4.07E-08 and P = 3.27E-04, respectively) the AVPR2 most commonly mutated amino acids. Alanine and glutamate are significantly (P = 0.009 and P = 0.019, respectively) the least mutated AVPR2 amino acids. The spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense. The AVPR2 mutations are spread world-wide. Our study may serve as an updated review, comprehensive of all AVPR2 variants and specific gene locations. J. Cell. Physiol. 217: 605-617, 2008. (c) 2008 Wiley-Liss, Inc.
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PMID:AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. 1872 98

Regulation of body water homeostasis occurs by the vasopressin-dependent sorting of aquaporin-2 (AQP2) water channels to and from the apical membrane of renal principal cells. Mutations in AQP2 cause autosomal nephrogenic diabetes insipidus (NDI), a disease that renders the kidney unresponsive to vasopressin, resulting in polyuria and polydipsia. The AQP2 mutant c.772G>A; p.Glu258Lys (AQP2-E258K) causes dominant NDI by oligomerizing with wild-type AQP2 and missorting of this AQP2 complex to multivesicular bodies instead of the apical membrane. The motif causing this missorting of AQP2-E258K was identified here. Functional analyses and plasma membrane expression studies of truncation mutants in oocytes revealed that AQP2-E258K shortened to Leu259 is still intracellular retained. Alanine scanning and glutamic acid to arginine exchanges revealed increased function and plasma membrane expression for AQP2-E258K mutants with the following additional changes: Leu259Ala, Arg252Glu, Arg253Glu, or Arg252Ala-Arg254Ala, or for the AQP2 mutant p.Glu258Ala, indicating that the motif RRRxxxK(258)L confers AQP2-E258K retention. Fusion of this motif to aquaporin-1 also resulted in missorting of that water channel, indicating that this retention motif is transferable. In conclusion, our data reveal that the RRRxxxKL motif and repulsion between K258 and the arginine-triplet within this motif are the primary cause of missorting of AQP2-E258K in NDI.
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PMID:Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus. 1970 45