title: Cytochrome P-450 metabolites in endothelin-stimulated cardiac hormone secretion.
abstract: We examined the role of cytochrome P-450-arachidonate (CYP450-AA) metabolites in endothelin-1 (ET-1)-stimulated atrial natriuretic peptide (ANP) and pro-ANP-(1-30) secretion from the heart. 17-Octadecynoic acid (17-ODYA, 10(-5) M) significantly inhibited ANP secretion stimulated by ET-1 (10(-8) M) in the isolated perfused rat atria and inhibited pro-ANP-(1-30) secretion stimulated by ET-1 (10(-8) M) or 20-hydroxyeicosatetraenoic acid in cultured neonatal rat ventricular myocytes (NRVM). In NRVM, 17-ODYA significantly (P < 0.05) increased secretion of cAMP but had no significant effect on the secretion of cGMP from NRVM. Staurosporine, an inhibitor of protein kinase C, completely blocked the inhibitory action of 17-ODYA, whereas a protein kinase A inhibitor, H-89 (5 x 10(-5) M), did not significantly attenuate the effects of 17-ODYA. The results show that the inhibitory action of 17-ODYA on ET-1-augmented ANP secretion is mediated through cAMP and suggest that CYP450-AA may play an important role in ET-1-induced cardiac hormone secretion.
authors.affiliation: Dept. of Physiology and Biophysics, University of South Florida, College of Medicine, Box 8, Tampa, FL 33612, USA.
authors.forename: Sook Jeong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Carol S
authors.initials: CS
authors.lastname: Landon
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Nazian
authors.forename: John R
authors.initials: JR
authors.lastname: Dietz
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C054547:atrial natriuretic factor prohormone (1-30), human; C047008:17-octadecynoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D009320:Atrial Natriuretic Factor; D003577:Cytochrome P-450 Enzyme System