'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart

Salvatore Pepe, Rui Ping Xiao, Charlene Hohl, Ruth Altschuld, Edward G. Lakatta

Research output: Contribution to journalArticle

Abstract

Background: Cardiac myocyte sarcolemma contains both catecholamine and opioid peptide receptors (OPRs). Opioid peptides are coreleased with catecholamines from nerve terminals in the heart. We investigated whether OPR stimulation influences the effects of β-adrenergic receptor (β-AR) stimulation in the isolated, isovolumic rat heart and whether the mechanism of such an interaction involves both β-AR subtypes or an alteration in β- AR-mediated increase in cAMP. Methods and Results: Norepinephrine (NE, 10- 7 mol/L) increased peak left ventricular systolic pressure (LVSP) and cAMP more than twofold compared with controls. The δ-OPR agonist leucine- enkephalin (LE, 10-8 mol/L) markedly inhibited the β1-AR-induced positive inotropic effect and increase in cAMP but alone had no effect on basal LVSP or basal cAMP levels. The OPR antagonist naloxone 108 mol/L added to LE+NE perfusate reversed the LE-induced decrease in cAMP and LVSP even though naloxone alone had no effect on LVSP and cAMP levels. LE could not counteract the twofold increase in LVSP produced by the nondegradable cAMP analog CPT- cAMP 2.3 x 10-5 mol/L or a high concentration of forskolin (10-7 mol/L) but did reverse the 173±11.8% and 135±13.6% increases in LVSP stimulated by 10-8 and 0.5x10-8 mol/L forskolin, respectively. LE inhibited cAMP production at all concentrations of forskolin (10-7, 10-8 and 0.5x10-8 mol/L). Pertussis toxin (PTX) pretreatment abolished LE effects on β1-AR stimulation. Zinterol 10-5 and 10-6 mol/L, a specific β2-AR agonist that elicits a cAMP-independent inotropic effect in rat heart, caused 225±14% and 182±5% increases in LVSP that could not be reversed by addition of LE. Conclusions: Potent, inhibitory 'cross talk' between δ-OPR and β1- AR signaling pathways occurs via a PTX-sensitive G(i/o) protein involved in adenylyl cyclase inhibition in rat heart.

Original languageEnglish (US)
Pages (from-to)2122-2129
Number of pages8
JournalCirculation
Volume95
Issue number8
DOIs
StatePublished - Apr 15 1997
Externally publishedYes

Keywords

  • adrenergic, beta
  • cAMP
  • opioid peptides
  • proteins
  • rats
  • receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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