Regulation of dna synthesis of myocardial and epicardial cells in
the developing rat heart by [met5]-enkephalin.
McLaughlin, Patricia J.
Department of Neuroscience and Anatomy, The Pennsylvania State
University, College of Medicine, Hershey, Pennsylvania 17033
APStracts 3:0029R, 1996.
Endogenous opioids serve as negative growth factors in neural and non
-neural tissues, in addition to being neuromodulators. This study
investigated the hypothesis that native opioid peptides are
inhibitory growth factors in heart development. DNA synthesis of
ventricular myocardial and epicardial cells in 1-day old rats was
examined. Administration of a variety of opioids and peptides
revealed that [Met5]-enkephalin had the greatest inhibitory effect on
DNA synthesis; peptides related to m, w, k, e, and s receptors had no
influence on cell proliferation, even at concentrations as high as 10
mg/kg. [Met5]-enkephalin, also termed opioid growth factor (OGF),
depressed DNA synthesis at 1 and 10 mg/kg, but not at 0.01 or 0.1
mg/kg. The effects of OGF were noted within 1 hour of treatment,
persisted for as long as 22 hours after drug administration, and
could depress DNA synthesis in myocardial and epicardial cells to 43%
and 36%, respectively, of control values. The effect of OGF on DNA
synthesis of heart cells was opioid receptor-mediated. Organ culture
experiments revealed that opioids acted directly on developing
cardiac cells. Both OGF, and its receptor, zeta (z), were detected in
heart cells of 1-day old rats by immunocytochemistry. Messenger RNA
for preproenkephalin, the precursor to OGF, was observed in 1-day old
rat heart. These results indicate that an autocrine/paracrine
produced endogenous opioid peptide (i.e., OGF), and its receptor
(i.e., z), are present in the developing heart and govern DNA
synthesis, with OGF acting directly as a tonic negative regulator of
cell generation.
Received 23 October 1995; accepted in final form 22 January 1995.
APS Manuscript Number R661-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96