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

We studied the urinary concentrating capacity in experimental hemochromatosis. Sprague-Dawley rats were randomized into iron (Fe)-loaded (injected sc with 1.2 g elemental iron/kg body weight as iron dextran) and pair-fed control groups. The urinary concentrating ability was studied after 10 months of iron loading. At basal condition, urine osmolality (Uosm) was significantly lower (P < 0.05) in the Fe-loaded rats compared with the control animals despite comparable urinary arginine-vasopressin (AVP) excretion in the two groups. Although 48-h water deprivation resulted in comparable rises in plasma concentration and urinary excretion of AVP in the two groups, maximal Uosm in the Fe-loaded animals was significantly lower than that seen in the control group (P < 0.01). Moreover, the observed urinary concentrating defect could not be corrected by pharmacological doses of exogenous AVP. There was no significant difference in renal chloride, sodium, calcium, or magnesium handling at either basal or sodium depleted states. Histologic studies showed marked iron deposition in the cortex and outer medulla accompanied by mild tubular atrophy particularly in the distal convoluted tubules. Thus, chronic experimental iron overload leads to nephrogenic diabetes insipidus marked by AVP-resistant urinary concentrating defect.
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PMID:Urinary concentrating defect in experimental hemochromatosis. 880 19

Vasopressin (VP) binds to the vasopressin type 2 receptor (V2R) to trigger physiological effects including body fluid homeostasis and blood pressure regulation. Signaling is terminated by receptor downregulation involving clathrin-mediated endocytosis and V2R degradation. We report here that both native and epitope-tagged V2R are internalized from the plasma membrane of LLC-PK1 kidney epithelial cells in the presence of another ligand, transferrin (Tf). The presence of iron-saturated Tf (holo-Tf; 4 h) reduced V2R binding sites at the cell surface by up to 33% while iron-free (apo-Tf) had no effect. However, no change in green fluorescent protein-tagged V2R distribution was observed in the presence of bovine serum albumin, atrial natriuretic peptide, or ANG II. Conversely, holo-Tf did not induce the internalization of another G protein-coupled receptor, the parathyroid hormone receptor. In contrast to the effect of VP, Tf did not increase intracellular cAMP or modify aquaporin-2 distribution in these cells, although addition of VP and Tf together augmented VP-induced V2R internalization. Tf receptor coimmunoprecipitated with V2R, suggesting that they interact closely, which may explain the additive effect of VP and Tf on V2R endocytosis. Furthermore, Tf-induced V2R internalization was abolished in cells expressing a dominant negative dynamin (K44A) mutant, indicating the involvement of clathrin-coated pits. We conclude that Tf can induce heterologous downregulation of the V2R and this might desensitize VP target cells without activating downstream V2R signaling events. It also provides new insights into urine-concentrating defects observed in rat models of hemochromatosis.
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PMID:Heterologous downregulation of vasopressin type 2 receptor is induced by transferrin. 2323 78