AJP - Regulatory, Integrative and Comparative Physiology, Vol 270, Issue 1 22-R32, Copyright © 1996 by American Physiological Society
Opioid growth factor-dependent DNA synthesis in the neonatal rat aorta
I. S. Zagon, Y. Wu and P. J. McLaughlin
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA.
In addition to neuromodulation, endogenous opioids serve as growth factors
in neural and nonneural 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 three 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 4-6 h 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 (zeta),
were associated with the cytoplasm of all three cell types in the neonatal
aorta. These results indicate that an endogenous opioid peptide (i.e., OGF)
and its receptor (i.e., zeta) 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.
