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Am J Physiol Renal Physiol (August 13, 2002). doi:10.1152/ajprenal.00245.2002
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Articles in PresS, published online ahead of print August 13, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00245.2002
Submitted on July 8, 2002
Accepted on August 5, 2002

Osmolality and solute composition are strong regulators of AQP2 expression in renal principal cells

Robert Storm1*, Enno Klussmann1, Andrea Geelhaar1, Walter Rosenthal2, and Kenan Maric1

1 Forschungsinstitut fur Molekulare Pharmakologie, Berlin, Brandenburg, Germany
2 Forschungsinstitut fur Molekulare Pharmakologie, Berlin, Brandenburg, Germany; Institut fur Pharmakologie, Freie Universitat Berlin, Berlin, Brandenburg, Germany

* To whom correspondence should be addressed. E-mail: storm{at}fmp-berlin.de.

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 here that osmolality and solute composition are potent regulators of AQP2 mRNA and protein synthesis besides the classical cAMP-dependent pathway, but do not affect the arginine-vasopressin (AVP)-induced AQP2 shuttle. In the presence of the cAMP-analogon dibuturyl-cAMP (Bt2cAMP, 500 µM), NaCl and sorbitol, but not urea evoked a robust increase of AQP2 expression in IMCD cells, with NaCl being far more potent than sorbitol. CREB phosphorylation increased with Bt2cAMP concentrations, but was not altered by changes in osmolality. In both, the rat and the human AQP2 promoter, we identified a putative tonicity-responsive element (TonE). We conclude, that in addition to the AVP/cAMP- signaling cascade, a further pathway activated by elevated effective osmolality (tonicity) is crucial for the expression of AQP2 in IMCD cells and suggest that the effect is mediated via TonE.




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