© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Cross-talk of opioid peptide receptor and β-adrenergic receptor signalling in the heart
aLaboratory of Cardiac Surgical Research, Wynn Domain, Baker Heart Research Institute and The Alfred Hospital, Monash University Faculty of Medicine, Melbourne, Australia
bLaboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
cThe Institute of Molecular Medicine and The Institute of Cardiovascular Sciences, Peking University, Beijing 100871, People's Republic of China
* Corresponding author. Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel.: +1-410-558-8662; fax: +1-410-558-8150. Email address: xiaor{at}grc.nia.nih.gov
Opioid peptide receptor (OPR) and β-adrenergic receptor (β-AR) are well-established members of G-protein-coupled receptor (GPCR) superfamily and are involved in regulating cardiac contractility, energy metabolism, myocyte survival or death. OPRs are typical Gi/Go-coupled receptors and activated by opioid peptides derived from the endorphin, dynorphin and enkephalin families, whereas β-AR stimulated by catecholamines is the model system for Gs-coupled receptors. While it is widely accepted that β-AR stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise, we have only begun to appreciate functional roles of OPR stimulation in regulating cardiovascular performance. Cardiovascular regulatory effects of endogenous opioids were initially considered to originate from the central nervous system and involved the pre-synaptic co-release of norepinephrine with enkephalin from sympathetic neuronal terminals in the heart. However, opioid peptides of myocardial origin have been shown to play important roles in local regulation of the heart. Notably, OPR stimulation not only inhibits cardiac excitation–contraction coupling, but also protects the heart against hypoxic and ischemic injury via activation of Gi-mediated signalling pathways. Further, OPRs functionally and physically cross-talk with β-ARs via multiple hierarchical mechanisms, including heterodimerization of these receptors, counterbalance of functional opposing G protein signalling, and interface at downstream signalling events. As a result, the β-AR-mediated positive inotropic effect and increase in cAMP are markedly attenuated by OPR activation in isolated cardiomyocytes as well as sympathectomized intact rat hearts. This brief review will focus on the interaction between β-AR and OPR and its potential physiological and pathophysiological relevance in the heart.
KEYWORDS G protein-coupled receptors; β-Adrenergic receptors; Opioid peptide receptors; Receptor dimerization; Cardiac contractility; Cardiac preconditioning
Time for primary review 21 days
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