D-glucose and NaCl enhance the expression of aquaporin-1: inhibition of both by cholera toxin.
OBJECTIVE
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(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(-7) M). Angiotensin II (10(-6) M and 10(-8) M), vasopressin (10(-8) M) and/or atrial natriuretic peptide (10(-8) M) did not affect AQP-1 expression. Hyperosmolar Reno-60 and Hypaque-76 contrast agents at 500 mosm/kg.H(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.
Jenq
Wheamei
W
Division of Nephrology and Hypertension, University of South Florida for Health Sciences, Tampa, FL 33612, USA. wjenq@hsc.usf.edu
Ramirez
German
G
Peguero
Alfredo
A
Cooper
Denise R
DR
Vesely
David L
DL
D000804:Angiotensin II / Q000494:pharmacology; D051398:Aquaporin 1; D020346:Aquaporins / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001693:Biological Transport, Active; D001789:Blood Group Antigens; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D003287:Contrast Media / Q000494:pharmacology; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D009995:Osmosis; D012965:Sodium Chloride / Q000494:pharmacology*
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D003287:Contrast Media; D000804:Angiotensin II; D001127:Arginine Vasopressin; D051398:Aquaporin 1; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D002772:Cholera Toxin; D005947:Glucose