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

Item Type:Article
Title:Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1
Creators Name:Piuhola, J. and Hammes, A. and Schuh, K. and Neyses, L. and Vuolteenaho, O. and Ruskoaho, H.
Abstract: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.
Keywords:Adrenomedullin, Natriuretic Peptides, Plasma Membrane Ca2+-ATPase, Animals, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
Publisher:American Physiological Society
Page Range:R699-R705
Date:1 January 2001
Official Publication:https://doi.org/10.1152/ajpregu.2001.281.3.R699
PubMed:View item in PubMed

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