D-Glucose and NaCl Enhance the Expression of Aquaporin-1: Inhibition of Both by Cholera Toxin.

Aim: To determine whether glucose, NaCl and/or cholera toxin modify the expression of aquaporin-1 (AQP-1) water channel. Methods: Aquaporin-1 gene expression was studied using primary cultures of human renal proximal tubule epithelial (HRPTE) cells. Results:D-Glucose and NaCl (500 mosm/kg·H[sub 2] O each) enhanced AQP-1 expression 2.4-fold (p < 0.05) and 4.0-fold (p < 0.01), respectively, which could be blocked 73 and 70% (p < 0.01), respectively, by cholera enterotoxin (10[sup –7] M). Angiotensin II (10[sup –6] M and 10[sup –8] M), vasopressin (10[sup –8] M) and/or atrial natriuretic peptide (10[sup –8] M) did not affect AQP-1 expression. Hyperosmolar Reno-60 and Hypaque-76 contrast agents at 500 mosm/kg·H[sub 2] O and isomolar Visipaque at 25% (v/v) concentration(s) also increased AQP-1 expression 3.8- to 5.0-fold (p < 0.01) in HRPTE cells which also were inhibited by cholera toxin from 41% (p < 0.05) to 71% (p < 0.01). AQP-1 was translocated from the cytosol to the membrane of HRPTE cells and hyperosmolarity enhanced this translocation 2.5-fold (p < 0.01). Conclusions: The increased urinary concentrating ability in proximal segment of the diabetic kidney associated with increased plasma glucose may be mediated via glucose’s ability to enhance AQP-1 expression, which leads to a more concentrated urine. The decrease in urinary flow secondary to cholera toxin exposure, on the other hand, may be mediated indirectly by cholera toxin’s inhibition of aquaoporin-1 gene expression.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]