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J Am Soc Nephrol 15: 2998-3005, 2004
© 2004 American Society of Nephrology
doi: 10.1097/01.ASN.0000145877.28811.82

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BASIC SCIENCE

Indomethacin Enhances Shuttling of Aquaporin-2 Despite Decreased Abundance in Rat Kidney

Soo Wan Kim*, Joon Wan Kim{dagger}, Ki Chul Choi*, Seong Kwon Ma*, YoonWha Oh{dagger}, Ju-Young Jung{ddagger}, Jin Kim{ddagger} and JongUn Lee{dagger}

Departments of *Internal Medicine and {dagger}Physiology, Chonnam National University Medical School, and {ddagger}Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Correspondence to Dr. JongUn Lee, Department of Physiology, Chonnam National University Medical School, 5 Hak-dong, Gwangju 501-746, Korea. Phone: +82 62 220 4262; Fax: +82 62 232 1242; E-mail: julee{at}chonnam.ac.kr

The effect of nonsteroidal antiinflammatory drugs on the regulation of aquaporin-2 (AQP2) water channels in the kidney was determined. Male Sprague-Dawley rats were injected with indomethacin (5 mg/kg twice a day intraperitoneally) for 2 d. The control group was injected with vehicle. The expression of AQP2 proteins was determined in the kidney by immunoblotting and immunohistochemistry. The expression of Gs{alpha} and type VI adenylyl cyclase was determined by immunoblotting. The activity of adenylyl cyclase complexes was determined by stimulated accumulation of cAMP. Immunoblotting revealed that indomethacin markedly decreased the expression of AQP2. Accordingly, however, the ratio of AQP2 expression in the membrane fraction versus that in the cytoplasmic fraction was increased. The urinary excretion of AQP2 proteins also increased. Immunohistochemistry demonstrated almost exclusive apical labeling of AQP2 with scanty cytoplasmic localization along the collecting duct. The expression of Gs{alpha} and adenylyl cyclase VI proteins was decreased. The generation of cAMP provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted. These results suggest that indomethacin increases the shuttling of AQP2 while it decreases its abundance in the collecting duct.




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