Zagon I S, Sassani J W, McLaughlin P J
Department of Neuroscience and Anatomy, Pennsylvania Lions Vision and Research Center, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA.
Am J Physiol. 1995 Apr;268(4 Pt 2):R942-50. doi: 10.1152/ajpregu.1995.268.4.R942.
In addition to neuromodulation, endogenous opioid peptides serve as growth factors. To determine involvement of opioids in the homeostatic renewal and repair of the corneal epithelium, epithelial outgrowths from 3-mm explants of rabbit cornea were investigated. Blockade of opioid-receptor interaction by the potent opioid antagonist naltrexone (NTX) for 7 days significantly increased the extent of outgrowths and the number and labeling index (DNA synthesis) of epithelial cells, relative to control levels. Outgrowths exposed to the opioid growth factor (OGF) [Met5]enkephalin for 7 days were subnormal in extent and labeling index and displayed alterations in architectural pattern. The effects of OGF on epithelial outgrowth were blocked by concomitant exposure to the opioid antagonist naloxone; naloxone alone had no effect on growth at the concentration utilized. NTX and OGF were active in both serum-containing and serum-free cultures. Immunocytochemical investigations showed that both OGF and its opioid receptor zeta (zeta) were present in epithelial cells growing in control media. The results indicate that an endogenous opioid peptide and its receptor are present in mammalian corneal epithelium and serve to modulate cell proliferation, migration, and organization.
除了神经调节作用外，内源性阿片肽还具有生长因子的功能。为了确定阿片类物质在角膜上皮的稳态更新和修复中的作用，对兔角膜3毫米外植体的上皮细胞生长进行了研究。强效阿片拮抗剂纳曲酮（NTX）阻断阿片受体相互作用7天，相对于对照水平，显著增加了生长范围、上皮细胞数量和标记指数（DNA合成）。暴露于阿片生长因子（OGF）[Met5]脑啡肽7天的外植体，其生长范围和标记指数低于正常水平，并表现出结构模式的改变。同时暴露于阿片拮抗剂纳洛酮可阻断OGF对上皮细胞生长的影响；在所使用的浓度下，单独使用纳洛酮对生长没有影响。NTX和OGF在含血清和无血清培养中均有活性。免疫细胞化学研究表明，OGF及其阿片受体ζ（ζ）均存在于对照培养基中生长的上皮细胞中。结果表明，内源性阿片肽及其受体存在于哺乳动物角膜上皮中，起到调节细胞增殖、迁移和组织的作用。
