Cytochrome P-450 metabolites in endothelin-stimulated cardiac hormone secretion

Department of Physiology and Biophysics and the University of South Florida, Cardiac Hormone Center, Tampa, Florida 33612 Submitted 22 August 2003 ; accepted in final form 6 January 2004 We examined the role of cytochrome P -450-arachidonate (CYP450-AA) metabolites in endothelin-1 (ET-1)-stimulated...

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Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2004-05, Vol.286 (5), p.R888-R893
Main Authors: Lee, Sook Jeong, Landon, Carol S, Nazian, Stanley J, Dietz, John R
Format: Article
Language:English
Subjects:
Animals
Atrial Natriuretic Factor - metabolism
Atrial Natriuretic Factor - secretion
Cells, Cultured
Cytochrome P-450 Enzyme System - metabolism
Endothelin-1 - pharmacology
Enzyme Inhibitors - pharmacology
Fatty Acids, Unsaturated - pharmacology
Hydroxyeicosatetraenoic Acids - pharmacology
In Vitro Techniques
Male
Myocardium - cytology
Myocardium - metabolism
Myocardium - secretion
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - secretion
Peptide Fragments - metabolism
Peptide Fragments - secretion
Protein Kinase Inhibitors
Rats
Rats, Sprague-Dawley
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Summary:Department of Physiology and Biophysics and the University of South Florida, Cardiac Hormone Center, Tampa, Florida 33612 Submitted 22 August 2003 ; accepted in final form 6 January 2004 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. endothelin-1; 20-hydroxyeicosatetraenoic acid; 17-octadecynoic acid; nitric oxide; protein kinase A; protein kinase C; atrial natriuretic peptide; pro-ANP-(1-30); cardiac hypertrophy Address for reprint requests and other correspondence: J. R. Dietz, Dept. of Physiology and Biophysics, Univ. of South Florida, College of Medicine, Box 8, Tampa, FL 33612 (E-mail: jdietz{at}hsc.usf.edu ).
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00482.2003