Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes

Sun, Qiang, Ma, Yi, Zhang, Lin, Zhao, Yu-Feng, Zang, Wei-Jin and Chen, Chen (2010) Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes. Endocrinology, 151 9: 4446-4454. doi:10.1210/en.2009-1432


Author Sun, Qiang
Ma, Yi
Zhang, Lin
Zhao, Yu-Feng
Zang, Wei-Jin
Chen, Chen
Title Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes
Formatted title
Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
2150-5810
Publication date 2010-09
Sub-type Article (original research)
DOI 10.1210/en.2009-1432
Volume 151
Issue 9
Start page 4446
End page 4454
Total pages 9
Editor Jeffrey D. Blaustein
Place of publication Chevy Chase, MD, U.S.A.
Publisher Endocrine Society
Collection year 2011
Language eng
Formatted abstract
Ghrelin and its synthetic analogue hexarelin are specific ligands of GH secretagogue receptor (GHS-R) and induce a variety of cardiovascular protective and cardiac positive inotropic effects. The signaling system underlying immediate effects of both GHSs in cardiomyocytes remains undefined. In the present study, we investigated the immediate effects of GHSs on isolated ventricular myocyte shortening, intracellular Ca2+ ([Ca2+]i) transients, and the L-type Ca2+ current (ICa,L). Putative intracellular signalling cascades were studied with specific receptor and signalling blockers. In fresh isolated adult Wistar rat ventricular myocytes, GHSs produced a positive inotropic effect in a concentration-dependent manner and increased the amplitude of [Ca2+]i transients and the ICa,L. The positive inotropic response was abolished by the GHS-R1a antagonist [D-Lys3]-GH-releasing peptide-6 (10 µM). GHS-induced increase in the ICa,L was abolished by [D-Lys3]-GH-releasing peptide-6 and protein kinase C inhibitor, chelerythrine chloride (5 µM), but not by protein kinase A inhibitor, KT 5720 (10 µM). We conclude that hexarelin and ghrelin increase the ICa,L, through GHS-R1a receptor and protein kinase C signalling cascade, which contribute to its direct positive inotropic effect on cardiomyocytes.
Copyright © 2010 by The Endocrine Society
Keyword Growth-hormone secretagogue
Heart-failure
Myocardial-infarction
Endothelial-cells
Ghrelin
Hexarelin
Peptides
Dysfunction
Cardiomyocytes
Modulation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Sun, 12 Sep 2010, 00:05:20 EST