Gentamicin decreases the abundance of aquaporin water channels in rat kidney.
The present study was performed to examine whether the gentamicin-induced urinary concentration defect is related to an altered regulation of aquaporin (AQP) water channels in the kidney. Male Sprague-Dawley rats were subcutaneously injected with gentamicin (20, 50 or 100 mg/kg per day) for 6 days. The protein expression of AQP1-3 channels and the catalytic activity of adenylyl cyclase were determined in the kidney. Gentamicin treatment resulted in renal failure associated with decreased tubular free water reabsorption and increased urinary flow rate. The expression of AQP2 proteins was significantly decreased in the kidney, in which the cortex was most susceptible, followed by the outer medulla and inner medulla in order. Gentamicin treatment also decreased the shuttling of AQP2, as evidenced by a decrease of its expression in the membrane fraction in proportion to that in the cytoplasmic fraction. The protein expression of AQP1 as well as that of AQP3 was also decreased in the cortex by treatment with the highest dose of gentamicin. The cAMP generation in response to arginine vasopressin or sodium fluoride was decreased by gentamicin, while that to forskolin was not significantly altered. These findings suggest that the primary impairment in the pathway leading to the generation of cAMP lies at the level of G proteins, resulting in a decreased expression of cAMP-mediated AQP channels. The gentamicin-induced urinary concentration defect may in part be accounted for by a reduced abundance of AQP water channels in the kidney.
Lee
J
J
Department of Physiology, Chonnam National University Medical School, Kwangju, Korea. julee@chonnam.ac.kr
Yoo
K S
KS
Kang
D G
DG
Kim
S W
SW
Choi
K C
KC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology
D000900:Anti-Bacterial Agents; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D005839:Gentamicins; D012076:Renal Agents; D001127:Arginine Vasopressin; D051398:Aquaporin 1; D051400:Aquaporin 3; D000242:Cyclic AMP