Cross-talk of opioid peptide receptor and β-adrenergic receptor signalling in the heart

Salvatore Pepe, Olivier W.V. Van Den Brink, Edward G. Lakatta, Rui Ping Xiao

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)414-422
Number of pages9
JournalCardiovascular research
Volume63
Issue number3
DOIs
StatePublished - Aug 15 2004
Externally publishedYes

Keywords

  • Cardiac contractility
  • Cardiac preconditioning
  • G protein-coupled receptors
  • Opioid peptide receptors
  • Receptor dimerization
  • β-Adrenergic receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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