RGD Reference Report - Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat kidney. - Rat Genome Database

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Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat kidney.

Authors: Kim, SW  Kim, JW  Choi, KC  Ma, SK  Oh, Y  Jung, JY  Kim, J  Lee, J 
Citation: Kim SW, etal., J Am Soc Nephrol. 2004 Dec;15(12):2998-3005.
RGD ID: 2313211
Pubmed: (View Article at PubMed) PMID:15579502
DOI: Full-text: DOI:10.1097/01.ASN.0000145877.28811.82

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.


Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Adcy6  (adenylate cyclase 6)
Aqp2  (aquaporin 2)
Gnas  (GNAS complex locus)

Genes (Mus musculus)
Adcy6  (adenylate cyclase 6)
Aqp2  (aquaporin 2)
Gnas  (GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus)

Genes (Homo sapiens)
ADCY6  (adenylate cyclase 6)
AQP2  (aquaporin 2)
GNAS  (GNAS complex locus)

Additional Information