title: Characteristics of the renal C-type natriuretic peptide receptor in hypertrophied and developing rat kidney.
abstract: 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[Gln(18), Ser(19), Gly(20), Leu(21), Gly(22)]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.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1752, USA. GeoffrreyW@intra.niddk.nih.gov
authors.forename: G E
authors.initials: GE
authors.lastname: Woodard
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: J A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006984:Hypertrophy; D007668:Kidney / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000494:pharmacology; D009392:Nephrectomy; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D020098:Natriuretic Peptide, C-Type; D005576:Colforsin; D012701:Serotonin; D006632:Histamine; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C