Opioid growth factor-dependent DNA synthesis in the neonatal rat aorta.

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.