Atriopeptin biochemical pharmacology.
Several low-molecular-weight peptides that possess potent natriuretic, diuretic, and vascular smooth muscle relaxant activity have been isolated from atrial extracts. Elucidation of their structure indicates that they consist of a 17-membered ring of amino acids formed by a cystine disulfide bond and that they differ only in the composition of the amino and carboxy termini. The 24-amino-acid peptide atriopeptin (AP) III was selected as the reference compound for structure-activity studies. Amino-terminal amino acid extensions on APIII markedly increase the natriuretic-diuretic but not the renal vasodilatory response in anesthetized dogs, which suggests a heterogeneity of AP receptors in renal tubular and vascular tissues. Radioligand (125I-labeled APIII) binding studies with fresh rat kidney slices indicate that the primary renal sites of specific AP binding are in the glomerulus and in the papillary segment of the medulla, thus implicating these structures in the natriuretic-diuretic effect. Data obtained from radioimmunoassay, chromatographic migration, vasorelaxant biological activity, and peptide sequence analysis indicate that Ser-Leu-Arg-Arg-APIII is the major circulating form of low-molecular-weight atrial peptide present in rat plasma. Circulating APs fulfill many of the criteria for involvement in the endocrine regulation of fluid and electrolyte homeostasis.
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001923:Brain Chemistry; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D006325:Heart Atria / Q000032:analysis; D007668:Kidney / Q000098:blood supply; D007678:Kidney Glomerulus / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008970:Molecular Weight; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D011863:Radioimmunoassay; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
D010446:Peptide Fragments; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP