Barg J, Belcheva M M, Levy R, McHale R J, McLachlan J A, Johnson F E, Coscia C J, Vogel Z
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Glia. 1994 Jan;10(1):10-5. doi: 10.1002/glia.440100103.
Treatment of rat C6 glioma cells with the tricyclic antidepressant desipramine induces opioid binding. Here the distribution of these opioid-binding sites on C6 cell membranes and a functional property were investigated. Immunohistochemical examination of C6 cells was performed using a monoclonal anti-idiotypic antibody to opioid receptors (Ab2AOR). Ab2AOR uniformly labeled > 97% of the cells exposed to desipramine over their entire surface. The opioid-receptor antagonist naltrexone completely blocked Ab2AOR binding. Ab2AOR, which has opioid agonist properties, also inhibited DNA synthesis in desipramine-treated but not in naive C6 cells. Similarly, morphine blocked C6 cell proliferation only after desipramine treatment. The antineurotrophic action of Ab2AOR was reversed by naltrexone and was insensitive to pertussis toxin. These findings demonstrate that Ab2AOR suppresses the proliferation of C6 glioma cells by binding to desipramine-induced opioid receptors.
用三环类抗抑郁药地昔帕明处理大鼠C6胶质瘤细胞可诱导阿片样物质结合。在此，研究了这些阿片样物质结合位点在C6细胞膜上的分布及其功能特性。使用抗阿片样物质受体的单克隆抗独特型抗体（Ab2AOR）对C6细胞进行免疫组织化学检查。Ab2AOR在整个表面均匀标记了超过97%暴露于地昔帕明的细胞。阿片样物质受体拮抗剂纳曲酮完全阻断了Ab2AOR的结合。具有阿片样物质激动剂特性的Ab2AOR也抑制了用地昔帕明处理的C6细胞的DNA合成，但对未处理的C6细胞无此作用。同样，吗啡仅在用地昔帕明处理后才阻断C6细胞增殖。Ab2AOR的抗神经营养作用可被纳曲酮逆转，且对百日咳毒素不敏感。这些发现表明，Ab2AOR通过与地昔帕明诱导的阿片样物质受体结合来抑制C6胶质瘤细胞的增殖。
