title: Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat kidney.
abstract: 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 G(salpha) 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 G(salpha) 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.
authors.affiliation: Department of Physiology, Chonnam National University Medical School, 5 Hak-dong, Gwangju 501-746, Korea.
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Joon Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Yoonwha
authors.initials: Y
authors.lastname: Oh
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: JongUn
authors.initials: J
authors.lastname: Lee
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000097:blood; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D014867:Water; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; D007213:Indomethacin