Opioid growth factor-dependent dna synthesis of endothelial, smooth
muscle, and fibroblast cells in the neonatal rat aorta.
Zagon, Ian S., Patricia J. McLaughlin, Yan Wu.
Department of Neuroscience and Anatomy, The Pennsylvania State
University College of Medicine, Hershey, Pennsylvania 17033
APStracts 2:0218R, 1995.
In addition to neuromodulation, endogenous opioids serve as growth
factors in neural and non-neural cells. This study examined the
hypothesis that opioids are inhibitory growth factors in vascular
development. No circadian rhythm was detected for DNA synthesis in
endothelial, smooth muscle, or fibroblast cells in the aorta of 1-day
old rats. Administration of naltrexone (NTX), a potent opioid
antagonist, markedly increased the labeling indexes of all 3 cell
types. [Met5]-enkephalin, found to be the only opioid peptide to
influence DNA synthesis and termed the opioid growth factor (OGF),
depressed DNA synthesis in each cell type for 4 to 6 hours in a dose
-dependent and receptor-mediated manner. In aortas placed in tissue
culture, DNA synthesis was significantly increased by incubation in
NTX, and decreased by incubation with OGF. Both OGF and its receptor,
zeta (z), were associated with the cytoplasm of all 3 cell types in
the neonatal aorta. These results indicate that an endogenous opioid
peptide (i.e., OGF) and its receptor (i.e., z) reside in the
developing vascular cells and govern DNA synthesis, with OGF acting
directly as a tonic negative regulator of cell generation in the
great vessels.
Received 15 February 1995; accepted in final form 14 July 1995.
APS Manuscript Number R118-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.