Zagon I S
Department of Anatomy, M.S. Hershey Medical Center, Pennsylvania State University, Hershey 17036.
Brain Res Bull. 1988 Nov;21(5):777-84. doi: 10.1016/0361-9230(88)90046-9.
Endogenous opioid systems participate in carcinogenic events. To understand further the action of opioids on growth, S20Y neuroblastoma cells in tissue culture were exposed to i) [Met5]-enkephalin, a naturally occurring opioid pentapeptide, at a concentration (10(-6) M) that inhibits cell replication by 66% of control levels, ii) [Met5]-enkephalin (10(-6) M) and the opioid antagonist naloxone (10(-6) M) which blocks opioid agonist action, or iii) naltrexone (10(-6) M), a potent antagonist that disrupts endogenous opioid-opioid receptor interaction and increased cell number 76% above control values. The morphology of cells exposed to these agents for 2-4 days were similar to controls (i.e., exposed to sterile water) as determined by scanning and transmission electron microscopy. These results support the hypothesis that endogenous opioid systems act as trophic factors as they regulate growth; their effects on cell growth and survival, however, do not alter the basic ultrastructural morphology of the cells. Moreover, these data strengthen the validity of paradigms and therapeutic regimens that utilize opioid agonists and antagonists to modulate the relationship of endogenous opioid-opioid receptor interactions in neural cancer.
内源性阿片系统参与致癌过程。为了进一步了解阿片类物质对生长的作用，将组织培养中的S20Y神经母细胞瘤细胞暴露于以下环境：i）[Met5]-脑啡肽，一种天然存在的阿片五肽，其浓度（10(-6) M）可使细胞复制抑制至对照水平的66%；ii）[Met5]-脑啡肽（10(-6) M）和可阻断阿片激动剂作用的阿片拮抗剂纳洛酮（10(-6) M）；或iii）纳曲酮（10(-6) M），一种强效拮抗剂，可破坏内源性阿片-阿片受体相互作用，使细胞数量比对照值增加76%。通过扫描电子显微镜和透射电子显微镜测定，暴露于这些试剂2 - 4天的细胞形态与对照（即暴露于无菌水中）相似。这些结果支持了以下假设：内源性阿片系统在调节生长时作为营养因子发挥作用；然而，它们对细胞生长和存活的影响并未改变细胞的基本超微结构形态。此外，这些数据强化了利用阿片激动剂和拮抗剂来调节神经癌中内源性阿片-阿片受体相互作用关系的范式和治疗方案的有效性。
