Opioid peptide receptor stimulation reverses β-adrenergic effects in rat heart cells

Rui Ping Xiao, Salvatore Pepe, Harold A. Spurgeon, Maurizio C. Capogrossi, Edward G. Lakatta

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Opioid peptide receptor (OPR) agonists are co-released with the β- adrenergic receptor (β-AR) agonist norepinephrine (NE) from nerve terminals in the heart during sympathetic stimulation. Whereas recent studies indicate that OPR and β-AR coexist on the surface of cardiac myocytes, whether significant 'cross talk' occurs between OPR and β-AR signaling cascades within heart cells is unknown. In the present study we demonstrate a marked effect of δ-OPR stimulation to modulate β-adrenergic responses in single isolated rat ventricular myocytes. Nanomolar concentrations (10-8 M) of the OPR agonist leucine enkephalin (LE), a naturally occurring δ-opioid peptide, inhibited NE-induced increases in sarcolemmal L-type Ca2+ current, cytosolic Ca2+ transient, and contraction. The antiadrenergic effect of LE was pertussis toxin sensitive and abolished by naloxone, an opioid receptor antagonist. In contrast, LE was unable to inhibit the positive inotropic effects induced by equipotent concentrations of 8-(4 chlorophenylthio)- adenosine 3',5'-cyclic monophosphate, a cell-permeant adenosine 3',5'-cyclic monophosphate analog, or by the non-receptor-induced increase in contraction by elevated bathing Ca2+ concentration. These results indicate that an interaction of the OPR and β-AR systems occurs proximal to activation of the adenosine 3',5'-cyclic monophosphate-dependent protein kinase of the β-AR intracellular signaling pathway. This modulation of β-adrenergic effects by OPR activation at the myocyte level may have important implications in the regulation of cardiac Ca2+ metabolism and contractility, particularly during the myocardial response to stress.

Original languageEnglish (US)
Pages (from-to)H797-H805
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2 41-2
StatePublished - Feb 1997
Externally publishedYes


  • calcium current
  • cardiac myocytes
  • contraction
  • intracellular calcium
  • β-adrenergic stimulation

ASJC Scopus subject areas

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


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