Indomethacin Enhances Shuttling of Aquaporin-2 Despite Decreased Abundance in Rat Kidney
| Title: | Indomethacin Enhances Shuttling of Aquaporin-2 Despite Decreased Abundance in Rat Kidney |
|---|---|
| Authors: | Kim, Soo Wan; Kim, Joon Wan; Choi, Ki Chul; Ma, Seong Kwon; Oh, YoonWha; Jung, Ju-Young; Kim, Jin; Lee, MD, PhD, JongUn |
| Publisher: | Journal of the American Society of Nephrology |
| Date Published: | December 01, 2004 |
| Reference Number: | 668 |
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.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The nonsteroidal anti-inflammatory drug indomethacin is often prescribed to reduce the increase in urine output associated with NDI, though how it increases the kidney’s urine concentrating ability is not fully understood. Kim, et al., conducted a series of experiments on the effect of indomethacin on the regulation of AQP2s in the kidney. The researchers had one experimental and one control group of rats. They injected the experimental group with indomethacin. The team observed that the experimental group of rats experienced a significantly decreased urinary flow rate even though the amount of AVP in their blood plasma and the concentration of particles in the serum was not significantly affected.
Kim, et al., determined the amount of AQP2 in the rats’ kidneys. They examined different sections of the kidney and found that after indomethacin treatment, there was a significant decrease in the number of AQP2 in the rats’ kidney cortex, outer medulla and inner medulla. Notably, even though the number of AQP2s decreased, the amount of AQP2s in the cell membrane, as opposed to the cell interior, was preserved. The researchers also note that in the experimental group of rats, several key aspects of the molecular sequence that stimulate AQP2 function, namely a specific G protein (Gsa) and adenylyl cyclase VI proteins were decreased. Also, the generation of cyclic adenosine monophosphate (cAMP), also part of the molecular sequence, was impaired. Thus, the total number of AQP2 in the experimental group’s kidneys decreased, yet the shuttling of the AQP2s to the apical cell membrane was increased, and this resulted in the decrease of urine volume found in these rats.