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Am J Physiol Regul Integr Comp Physiol 281: R699-R705, 2001;
0363-6119/01 $5.00
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Vol. 281, Issue 3, R699-R705, September 2001

Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1

Jarkko Piuhola1, Annette Hammes2, Kai Schuh3, Ludwig Neyses3, Olli Vuolteenaho4, and Heikki Ruskoaho1

Departments of 1 Pharmacology and Toxicology and 4 Physiology, Biocenter Oulu, FIN-90014 University of Oulu, Finland; 2 Max-Delbrück Center for Molecular Medicine, 13092 Berlin; and 3 Department of Medicine, University of Würzburg, D-97080 Würzburg, Germany

The function of the plasma membrane calmodulin-dependent calcium ATPase (PMCA) in myocardium is unknown. PMCA is localized in caveolae, 50- to 100-nm membrane invaginations, which also contain receptors for endothelin-1 (ET-1) and various other ligands. PMCA has been suggested to play a role in regulation of caveolar signal transduction. We studied the effects of the hypertrophic agonist ET-1 and increased coronary perfusion pressure on cardiac synthesis of B-type natriuretic peptide (BNP) in transgenic rats overexpressing the human PMCA 4CI in isolated perfused heart preparation. ET-1 infusion for 2 h increased BNP mRNA levels twofold in left ventricles (LV) of nontransgenic rats, whereas no increase was noted in PMCA rat hearts. Similar responses were seen in adrenomedullin and c-fos mRNA levels, and in immunoreactive BNP secretion. Increased mechanical load produced by elevated perfusion pressure induced similar 1.5- to 1.6-fold increases in LV BNP mRNA in both nontransgenic and PMCA rat hearts. These results show that cardiac overexpression of PMCA attenuates ET-1-stimulated early induction of cardiac gene expression, suggesting that PMCA may modulate myocardial growth responses.

plasma membrane Ca2+-ATPase; natriuretic peptides; adrenomedullin


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