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¹ National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1752, USA
² Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
³ Department of Physiology, University of Extremadura, Cáceres, Spain

(Requests for offprints should be addressed to G E Woodard; Email: GeoffreyW{at}intra.niddk.nih.gov)

This study investigates the effect of hypertrophy, using one kidney and one kidney/one clip rats, and development, comparing 3- and 12-week-old rats, on the expression of the 28-amino acid atrial natriuretic peptide (ANP_1–28) binding sites in rat kidney. Here we report an increased B_max value of glomerular binding sites for ANP_1–28 and C-type natriuretic peptide 1–22 (CNP_1–22) in hypertrophied and developing kidney, without modifying their affinity, an effect that was prevented in the presence of the synthetic des[Gln¹⁸, Ser¹⁹, Gly²⁰, Leu²¹, Gly²²]ANP_4–23-amide (C-ANF), suggesting that natriuretic peptide receptor (NPR)-C binding sites might be enhanced. The enhanced B_max was only detected in the high affinity binding site for CNP_1–22, which has been identified as the 67 kDa NPR-C-like protein. A similar effect was observed in renal glomeruli from 3-week-old rats compared with 12-week-old rats. Our results indicate that ANP_1–28, CNP_1–22 and C-ANF inhibited cAMP synthesis stimulated by the physiological agonists histamine and 5-hydroxytryptamine or directly by forskolin. The inhibitory effect was found to be significantly greater in 1-kidney and 1-kidney/1-clip rats than in controls, and in 3-week-old rats compared with 12-week-old rats. Our observations suggest that this effect must be attributed to the 67 kDa NPR-C-like protein due to the enhanced B_max values and the reported inhibitory role for this receptor on adenylyl cyclase activity. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis in hypertrophied and developing kidney may influence glomerular function in the rat kidney and suggests a role for the 67 kDa NPR-C-like protein in growth.

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