Ghrelin and synthetic growth hormone secretagogues are cardioactive molecules with identities and differences.
Ghrelin, a 28-amino acid peptide mainly produced by the stomach, is a natural ligand of the type 1a growth hormone secretagogue receptor (GHS-R1a) that also binds synthetic peptidyl and nonpeptidyl GHSs. GHS-R1a and various GHS-R1a-related receptor subtypes are widely distributed in central and peripheral tissues, particularly in the cardiovascular system. In agreement with this distribution of GHS-R, ghrelin and synthetic GHSs exert a wide spectrum of actions, including cardiac and vascular activities. Ghrelin, as well as peptidyl and nonpeptidyl GHSs, is able to increase cardiac performances both in animals and in humans and to exert protective effects on ischemia/reperfusion injury of isolated rat heart. Moreover, both ghrelin and synthetic GHSs have been shown as able to act as survival factors, protecting cardiomyocytes and endothelial cells from doxorubicin-induced apoptosis. Despite the fact that the neuroendocrine actions of ghrelin are dependent on its acylation in serine 3, these cardiovascular effects are exerted by unacylated as well as by acylated ghrelin. This evidence indicates that these actions are not likely to be mediated by a type 1a GHS-R, which, by definition, binds acylated ghrelin only. However, synthetic peptidyl GHSs, but not nonpeptidyl, and even ghrelin itself are able to reduce atherosclerotic lesion development in apolipoprotein-E-deficient mice. This action seems to be mediated by a specific receptor for synthetic peptidyl GHSs only, identified as CD36, a multifunctional B-type scavenger receptor involved in atherogenesis and mainly expressed in cardiomyocytes and microvascular endothelial cells. Thus, there are similarities, but also differences, between ghrelin and synthetic GHSs, in terms of cardiac actions that are likely to be related to the existence of multiple GHS-R subtypes that mediate the cardiovascular actions of the above substances. These actions indicate their potential pharmacotherapeutic implications in cardiovascular diseases.
Benso
Andrea
A
Department of Clinical and Biological Sciences, University of Turin and San Luigi Hospital, Orbassano, Turin, Italy.
Broglio
Fabio
F
Marafetti
Lisa
L
Lucatello
Barbara
B
Seardo
Maria Angela
MA
Granata
Riccarda
R
Martina
Valentino
V
Papotti
Mauro
M
Muccioli
Giampiero
G
Ghigo
Ezio
E
D000818:Animals; D001665:Binding Sites; D002320:Cardiovascular Physiological Phenomena; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D010210:Papillary Muscles / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D054440:Receptors, Ghrelin; D012039:Regional Blood Flow / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin