title: Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli.
abstract: This study investigates the effect of water deprivation on the expression of atrial natiruretic peptide (ANP)(1-28) binding sites in rat kidney. Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced. Our results indicate that ANP(1-28), CNP(1-22), 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 suggest that this effect must be attributed to the 67-kDa NPR-C-like protein, because the 67- and 77-kDa NPR-C-like proteins show high and low affinities for CNP(1-22), 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 ANP(1-28). Finally, we have found that ligand binding to the 67-kDa NPR-C-like protein is reduced by GTPgammaS, 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.
authors.affiliation: National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bldg. 10, Rm. 8C-208, 10 Center Dr., MSC 1752, Bethesda, MD 20892-1752, USA. GeoffreyW@intra.niddk.nih.gov
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Woodard
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000378:metabolism*; D008024:Ligands; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism* / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D014868:Water Deprivation / Q000502:physiology*
chemical_list: C072551:HS 142-1; D007457:Iodine Radioisotopes; D008024:Ligands; D011134:Polysaccharides; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor