title: Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes.
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 Ca(2+) ([Ca(2+)](i)) transients, and the L-type Ca(2+) current (I(Ca,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 [Ca(2+)](i) transients and the I(Ca,L). The positive inotropic response was abolished by the GHS-R1a antagonist [D-Lys(3)]-GH-releasing peptide-6 (10 microm). GHS-induced increase in the I(Ca,L) was abolished by [D-Lys(3)]-GH-releasing peptide-6 and protein kinase C inhibitor, chelerythrine chloride (5 microm), but not by protein kinase A inhibitor, KT 5720 (10 microm). We conclude that hexarelin and ghrelin increase the I(Ca,L), through GHS-R1a receptor and protein kinase C signalling cascade, which contribute to its direct positive inotropic effect on cardiomyocytes.
authors.affiliation: Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Zhao
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000502:physiology; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002227:Carbazoles; D004791:Enzyme Inhibitors; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D011758:Pyrroles; D054440:Receptors, Ghrelin; C086184:hexarelin; C057416:KT 5720; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium