Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1.
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.
Piuhola
J
J
Department of Pharmacology and Toxicology, Biocenter Oulu, FIN-90014 University of Oulu, Finland.
Hammes
A
A
Schuh
K
K
Neyses
L
L
Vuolteenaho
O
O
Ruskoaho
H
H
D053607:Adrenomedullin; D000818:Animals; D030801:Animals, Genetically Modified; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D021941:Caveolae / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010477:Perfusion; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical
D019332:Endothelin-1; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D000252:Calcium-Transporting ATPases