Zagon I S, Wu Y, McLaughlin P J
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Am J Physiol. 1996 Jan;270(1 Pt 2):R22-32. doi: 10.1152/ajpregu.1996.270.1.R22.
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.
除了神经调节作用外，内源性阿片肽在神经细胞和非神经细胞中还充当生长因子。本研究检验了阿片肽是血管发育中抑制性生长因子这一假说。在1日龄大鼠的主动脉中，未检测到内皮细胞、平滑肌细胞或成纤维细胞中DNA合成的昼夜节律。强效阿片拮抗剂纳曲酮（NTX）的给药显著增加了所有这三种细胞类型的标记指数。[Met5]脑啡肽被发现是唯一影响DNA合成的阿片肽，被称为阿片生长因子（OGF），它以剂量依赖和受体介导的方式在每种细胞类型中抑制DNA合成4 - 6小时。在置于组织培养中的主动脉中，DNA合成在NTX孵育时显著增加，而在与OGF孵育时减少。OGF及其受体ζ均与新生主动脉中所有三种细胞类型的细胞质相关。这些结果表明，一种内源性阿片肽（即OGF）及其受体（即ζ）存在于发育中的血管细胞中并调控DNA合成，OGF直接作为大血管中细胞生成的一种紧张性负调节因子。
