title: Enzymatic inactivation of major circulating forms of atrial and brain natriuretic peptides.
abstract: We compared the enzymatic inactivation of major circulating forms of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Both ANP and BNP induced a significant increase in cyclic GMP (cGMP) formation in cultured epithelial cell line derived from porcine kidney, LLC-PK1. The cGMP formation stimulated by ANP in LLC-PK1 cells was significantly decreased by pre-treatment of the peptide with rat renal brush-border membranes, and the inactivation of ANP was inhibited by neutral endopeptidase inhibitors, phosphoramidon and S-thiorphan. BNP exhibited greater resistance to enzymatic inactivation than did ANP. In addition, phosphoramidon potentiated the natriuresis with a low dose (7.5 pmol min(-1) kg(-1)) of ANP but not of BNP in rats. These results suggest that enzymatic degradation of natriuretic peptides is highly dependent on peptide structure, and that the affinity of BNP to neutral endopeptidase is less than that of ANP.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: K
authors.initials: K
authors.lastname: Inui
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D018929:Cell Culture Techniques; D006152:Cyclic GMP / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D018374:LLC-PK1 Cells; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D015260:Neprilysin / Q000502:physiology; D009578:Nitrobenzenes / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D015244:Thiorphan / Q000494:pharmacology
chemical_list: D006020:Glycopeptides; D009578:Nitrobenzenes; D011480:Protease Inhibitors; C110057:4-nitrophenethyl bromide; D009320:Atrial Natriuretic Factor; D015244:Thiorphan; D015260:Neprilysin; D006152:Cyclic GMP; C008890:phosphoramidon