ENDOGENOUS OPIOIDS REGULATE CELL-PROLIFERATION IN THE RETINA OF DEVELOPING RAT
ENDOGENOUS OPIOIDS REGULATE CELL-PROLIFERATION IN THE RETINA OF DEVELOPING RAT
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DOI：
10.1016/0006-8993(91)90887-2
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发表时间：
1991-03-22
期刊：
影响因子：
2.9
通讯作者：
ZAGON, IS
中科院分区：
文献类型：
--
作者：
ISAYAMA, T;MCLAUGHLIN, PJ;ZAGON, IS
内源性阿片类物质和阿片受体（内源性阿片系统）在调节细胞增殖的哺乳动物视网膜发育中的作用进行了检查在1日龄大鼠。与对照动物的标记指数（LI）35.8%相反，给予阿片肽[Met 5]-脑啡肽（100 μ g/kg）显著降低（10.6%）掺入[H-3]胸苷的细胞比例;同时注射1 mg/kg纳洛酮阻断[Met 5]-脑啡肽对细胞分裂的抑制作用。纳洛酮（1 mg/kg）单独给药不改变LI。纳洛酮（50 mg/kg）（一种强效阿片拮抗剂）中断内源性阿片-阿片受体相互作用，伴随着LI相对于对照水平显著增加（6.4%）。免疫细胞化学实验显示存在脑啡肽样免疫反应性，与染色的皮质细胞质的增殖和分化的视网膜细胞记录，没有免疫反应性在成人视网膜。使用I-125-[Met 5]-脑啡肽的体外放射自显影表明，[Met 5]-脑啡肽结合位点位于发育中的视网膜中;在成人视网膜中未记录到放射性标记配体的结合。这些结果表明，生长相关的内源性阿片类物质和阿片受体的存在下，在发展中的哺乳动物视网膜，但不是在成人视网膜，并表明，内源性阿片类物质作为天然的抑制性热带因子，紧张性调节细胞增殖。
The role of endogenous opioids and opioid receptors (endogenous opioid systems) in modulating cell proliferation in the developing mammalian retina was examined in 1-day-old rats. In contrast to a labeling index (LI) of 35.8% in control animals, administration of the opioid peptide [Met5]-enkephalin (100-mu-g/kg) significantly reduced (10.6%) the proportion of cells incorporating [H-3]thymidine; concomitant injection of 1 mg/kg naloxone blocked the inhibitory effects of [Met5]-enkephalin on cell division. Naloxone (1 mg/kg) alone did not alter the LI. The interruption of endogenous opioid-opioid receptor interaction by naltrexone (50 mg/kg), a potent opioid antagonist, was accompanied by a significant increase (6.4%) in the LI relative to control levels. Immunocytochemical experiments revealed the presence of enkephalin-like immunoreactivity, with staining of the cortical cytoplasm of proliferating and differentiating retinal cells recorded; no immunoreactivity was noted in the adult retina. In vitro autoradiography using I-125-[Met5]-enkephalin indicated that [Met5]-enkephalin binding sites were localized in the developing retina; no binding of the radiolabeled ligand was recorded in the adult retina. These results demonstrate the presence of growth-related endogenous opioids and opioid receptors in the developing mammalian retina, but not in adult retina, and suggest that endogenous opioids serve as natural inhibitory tropic factors that tonically regulate cell proliferation.