Opioid peptide receptor stimulation reverses [beta]-adrenergic
effects in rat heart cells.
Xiao, Rui-Ping, Salvatore Pepe, Harold A. Spurgeon, Maurizio C.
Capogrossi, and Edward G. Lakatta.
Laboratory of Cardiovascular Science, Gerontology Research Center,
National Institute on Aging, Baltimore, Maryland 21224
APStracts 3:0362H, 1996.
Opioid peptide receptor (OPR) agonists are co-released with the
[beta]-adrenergic receptor ([beta]AR) agonist, norepinephrine (NE),
from nerve terminals in the heart during sympathetic stimulation.
While recent studies indicate that OPR and [beta]AR both coexist on
the surface of cardiac myocytes, whether significant "cross
-talk" occurs between OPR and [beta]AR signaling cascades within
heart cells is unknown. In the present study, we demonstrate a marked
effect of [delta]-OPR stimulation to modulate [beta]-adrenergic
responses in single isolated rat ventricular myocytes. Nanomolar
concentrations (10-8 M) of the OPR agonist, leucine enkephalin (LE),
a naturally occurring [delta]-opioid peptide, inhibited NE-induced
increases in sarcolemmal L-type Ca2+ current (ICa), cytosolic Ca2+
(Cai) 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 chloro-phenylthio) cyclic AMP (CPT-cAMP), a cell permeant cAMP
analogue, or by the non-receptor-induced increase in contraction by
elevated bathing [Ca2+]. These results indicate that an interaction
of the OPR and [beta]AR systems occurs proximal to activation of the
cAMP-dependent protein kinase of the [beta]AR intracellular signaling
pathway. This modulation of [beta]-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.
Received 14 February 1996; accepted in final form 9 August 1996.
APS Manuscript Number H149-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996