Osmolality and Solute Composition are Strong Regulators of AQP2 Expression in Renal Principal Cells
| Title: | Osmolality and Solute Composition are Strong Regulators of AQP2 Expression in Renal Principal Cells |
|---|---|
| Authors: | Storm, Robert; Klussmann, Enno; Geelhaar, Andrea; Rosenthal, Walter; Maric, Kenan |
| Publisher: | American Journal of Physiology: Renal Physiology |
| Date Published: | January 01, 2003 |
| Reference Number: | 572 |
The water permeability of the renal collecting duct is regulated by the insertion of aquaporin-2 (AQP2) into the apical plasma membrane of epithelial (principal) cells. Using primary cultured epithelial cells from the inner medulla of rat kidney (IMCD cells), we show that osmolality and solute composition are potent regulators of AQP2 mRNA and protein synthesis, as well as the classical cAMP-dependent pathway, but do not affect the arginine vasopressin-induced AQP2 shuttle. In the presence of the cAMP analog dibutyryl cAMP (DBcAMP, 500 microM), NaCl and sorbitol, but not urea, evoked a robust increase of AQP2 expression in IMCD cells, with NaCl being far more potent than sorbitol. cAMP-responsive element-binding protein phosphorylation increased with DBcAMP concentrations but was not altered by changes in osmolality. In the rat and human AQP2 promoter, we identified a putative tonicity-responsive element. We conclude that, in addition to the arginine vasopressin/cAMP-signaling cascade, a further pathway activated by elevated effective osmolality (tonicity) is crucial for the expression of AQP2 in IMCD cells, and we suggest that the effect is mediated via the tonicity-responsive element.
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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.
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Storm, et al., developed a laboratory cell culture that allows sustained biosynthesis of AQP2. They used this culture to examine what factors, other than the AVP-initiated molecular sequence mentioned above, regulate the long-term expression of AQP2 in kidney collecting duct cells. They focused on two things: the osmolality of the solution surrounding the kidney collecting duct cell, and the type of particles in that solution. Osmolality is a measure of the concentration of particles in a solution. A highly concentrated solution will have a high osmolality. That is, it will have more particles per unit of solvent than a solution with a low osmolality.
Storm, et al., discovered that the generation of AQP2s in the collecting duct cell is dependent on the osmolality of the solution surrounding it. To a point, the higher the osmolality of the surrounding solution, the more AQP2 is generated. They also found that the type of particles (solutes) in the solution influence AQP2 expression. When the extracellular solution achieved its high osmolality due to a high concentration of sodium chloride (Na Cl) and urea, there was a significant increase of AQP2 expression in the cells. The research team further noted that though osmolality and solute composition do regulate the number of AQP2s generated, they do not affect the movement of the AQP2s from the cell interior to the cell membranes as does that other regulator of AQP2 generation, the AVP stimulated molecular sequence.
Storm et al., suggest that long term regulation of AQP2 by elevated osmolality is mediated by a section within the promoter region of the AQP2 gene called the tonicity responsive enhancer (TonE).