Document Detail

Modulation of myocardial contractility by lysophosphatidic acid (LPA).
MedLine Citation:
PMID:  12623301     Owner:  NLM     Status:  MEDLINE    
Lysophosphatidic acid (LPA) is a phospholipid messenger, which is released from activated platelets and leukocytes. This study examined the effects of LPA on myocardial contractility and characterized the signal transduction pathway involved in these effects. Functional effects of LPA were determined in isolated, electrically driven human myocardial preparations and rat cardiac myocytes. In human atrial and ventricular myocardial preparations, LPA (100 micromol/l) decreased isoprenaline (0.03 micromol/l) enhanced force of contraction by 17 +/- 2% and 28 +/- 3%, respectively. The effect of LPA was attenuated by suramin (1 mmol/l). In isolated rat cardiomyocytes, LPA (1-100 micromol/l) concentration dependently abolished isoprenaline (0.03 micromol/l) induced increase in cell shortening. This antiadrenergic effect was blunted after pretreatment with pertussis toxin (5 microg/ml, 12 h). Forskolin (10 micromol/l) stimulated adenylyl cyclase activity was inhibited by LPA in human myocardial membranes. PCR analysis of human atrial and ventricular cDNAs revealed the expression of two cognate LPA receptors: EDG-2 and EDG-7. Our results suggest that LPA exerts antiadrenergic effects on force of contraction in human and rodent myocardium via a Galpha(i/o) protein-mediated mechanism, most probably by LPA binding to the mammalian LPA receptors EDG-2 and/or EDG-7. This newly discovered action of LPA might be of pathophysiological importance in conditions like myocardial ischemia or inflammatory disorders when LPA release is enhanced.
Bodo Cremers; Markus Flesch; Evi Kostenis; Christoph Maack; Anke Niedernberg; Alexander Stoff; Michael Südkamp; Olaf Wendler; Michael Böhm
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  35     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-03-07     Completed Date:  2003-09-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  71-80     Citation Subset:  IM    
Medizinische Klinik und Poliklinik, Innere Medizin III,Universitätskliniken des Saarlandes, 66421, Homburg, Germany.
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MeSH Terms
Adenylate Cyclase / metabolism
Lysophospholipids / metabolism*
Myocardial Contraction / drug effects,  physiology*
Myocytes, Cardiac / enzymology,  metabolism
Pertussis Toxin / pharmacology
Receptors, Cell Surface / metabolism
Receptors, G-Protein-Coupled*
Receptors, Lysophospholipid
Suramin / pharmacology
Reg. No./Substance:
0/Lysophospholipids; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Receptors, Lysophospholipid; 145-63-1/Suramin; EC Toxin; EC Cyclase

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