Lithium-induced Down regulation of Aquaporin-2 Water Channel Expression in Rat Kidney Medulla
|Title:||Lithium-induced Down regulation of Aquaporin-2 Water Channel Expression in Rat Kidney Medulla|
|Authors:||Marples, David; Christensen, Sten; Christensen, Erik Ilso; Ottosen, Peter D.; Nielsen, Soren|
|Publisher:||Journal of Clinical Investigation|
|Date Published:||April 01, 1995|
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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 molecular basis of lithium-induced NDI is not yet clearly understood. Marples, et al., used rats as subjects to investigate the effect of lithium use on the expression of AQP2. The researchers found that in rats fed lithium there was a sharp reduction in the amount of AQP2 expressed in the kidney collecting duct cells. These reduced numbers of AQP2 were accompanied by the development of severe polyuria.
This reduction in AQP2 was only partly reversed when the rats were returned to a lithium-free diet. One week after the experimental rats were taken off the lithium diet, their AQP2 expression remained well below the control group's. This is consistent with clinical observations that show patients take several weeks to regain their normal urinary concentrating ability after cessation of chronic lithium therapy. However, the researchers found that depriving lithium-fed rats of water for two days increased AQP2 expression in the little sacs within the kidney collecting duct cells six-fold, even though they were still continuing lithium. And administering a form of synthetic VP over a seven day period increased AQP2 expression three-fold. In both cases, these increases represented only a partial reversal of the lithium-induced reduction in AQP2. This partial increase was accompanied by a partial increase in the ability to concentrate urine.