Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of diphenylamine to rats induces an acquired form of cystic disease. In order to examine the early changes in this model of experimental cystic disease prior to the development of the more severe structural alterations, clearance, micropuncture, and morphologic studies were performed in rats fed DPA for 3 to 6 weeks. A significant defect in maximal urine concentrating ability (Umax) was manifest by the second week and averaged 50% of control values. Further studies were undertaken to examine the cause of the defect in Umax. Whole-kidney glomerular filtration rate (GFR), single-nephron GFR, end-proximal TF/Pinulin, glucose and bicarbonate reabsorption were all normal, indicating normal function of the proximal tubule. Free water clearance and free water reabsorption were not significantly different in DPA-treated rats as compared to controls, suggesting normal function of the ascending limb of the loop of Henle and collecting duct. Morphologic examination revealed gross cysts in less than 10% of the kidneys but structural changes were consistently demonstrated in the collecting ducts of DPA-treated rats. These studies indicate that the decrease in Umax in DPA-treated animals is the result of a defect located at the terminal portion of the collecting duct.
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PMID:Renal function in experimental cystic disease of the rat. 95 92

Aquaporin-2 (AQP-2), a water channel located on the apical membrane of collecting duct cells, regulates water reabsorption under the control of vasopressin (AVP). Using an antibody directed to human AQP-2, a quantitative Western blot analysis was performed to determine the collecting duct responsiveness to an oral, nonpeptide, V2 receptor antagonist (VPA-985) in patients with chronic NYHA II and III heart failure. Standards were derived by conjugating the immunizing peptide to maleimide-activated bovine serum albumin and a standard curve was generated for each blot. Quantification of baseline steady-state AQP-2 excretion was done by collecting urine on the day before study drug administration. The next day patients received either placebo or VPA-985 at one of four different doses and urine was collected every 2 h. Thereafter, urinary AQP-2 excretion was calculated as a ratio of the urine flow and was expressed in pmol/h. During baseline, steady-state excretion did not change significantly (T0-T2, 458 +/- 44; T2-T4, 443 +/- 35; T4-T6, 422 +/- 35; T6-T8, 401 +/- 30). Compared to placebo, urinary AQP-2 excretion decreased significantly and in all groups in a dose-dependent manner during VPA-985 administration. The most impressive decrease was observed in the 250-mg group (T0-T2, 89 +/- 5; T2-T4, 50 +/- 18; T4-T6, 43 +/- 22; T6-T8, 42 +/- 23; P < 0.001 during each period compared with baseline and placebo results). VPA-985 significantly increased solute-free water clearance and urine output and significantly decreased urinary osmolality. Urinary AQP-2 excretion correlated best with solute-free water clearance during T0-T2 and T2-T4 collection, but a correlation with urinary osmolality and urinary output was also found during these periods. In conclusion, AQP-2 urinary excretion, as measured by quantitative Western analysis, is a sensitive biologic marker to assess the short-term responsiveness of the collecting duct to a V2 receptor AVP antagonist in chronic heart failure.
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PMID:Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure. 1050 93