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Am J Physiol Renal Physiol (May 4, 2004). doi:10.1152/ajprenal.00069.2004
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Submitted on March 2, 2004
Accepted on April 27, 2004

Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli

Geoffrey E. Woodard1*, Xiaohong Li2, and Juan A. Rosado3

1 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
2 Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
3 Department of Physiology, University of Extremadura, Caceres, Spain

* To whom correspondence should be addressed. E-mail: gew232000{at}yahoo.com.

This study investigates the effect of water deprivation on the expression of ANP1-28 binding sites in rat kidney. Water deprivation increased the Bmax of glomerular binding sites for ANP1-28 and CNP1-22 without modifying their affinity, an effect that was prevented in the presence of C-ANF, suggesting that NPR-C binding sites might be enhanced. Our results indicate that ANP1-28, CNP1-22 and C-ANF inhibit cAMP synthesis directly stimulated by forskolin or by the physiological agonists histamine and 5-hydroxytryptamine . The inhibitory effect was found to be significantly greater in water deprived rats than in controls. Our observations suggests that this effect must be attributed to the 67 kDa NPR-C-like protein, since the 67 and 77 kDa NPR-C-like proteins show high and low affinities for CNP1-22, respectively, and the enhanced inhibitory effect of CNP on cAMP generation in water deprived rats was detected at subnanomolar concentrations. In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67 kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77 kDa NPR-C-like but not the 67 kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP1-28. Finally, we have found that ligand binding to the 67 kDa NPR-C-like protein is reduced by GTP{gamma}S, suggesting that this receptor is associated with a G protein in renal glomeruli. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis induced by water deprivation may influence glomerular function in the rat kidney.




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