SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC

A）胃泌素释放肽受体：模型系统。 胃泌素释放 肽是衍生自proGRP前体的27个氨基酸的肽， 其中至少有三种类型的不同， 在不涉及GRP的位置在前体的3'端剪接 分子的一部分。 为了研究GRP受体GH3细胞的性质，克隆了一种克隆大鼠GH3细胞， 垂体细胞系表现出增强的磷酸肌醇周转， 对蛙皮素结合的反应。 该过程对以下因素部分敏感： 低至0.15 μ M蛙皮素也能诱发百日咳毒素。 对 研究SCLC培养，初步实验表明，一个小的，但 添加蛙皮素后在磷酸肌醇转换中可再现的肿瘤 一种已知有受体的细胞系。 交联剂已用于确认标记的 GRP到GH3和3T3细胞，并将用于进一步尝试 表征并可能纯化GRP受体。 B。鸟嘌呤核苷酸调节蛋白与肺癌的关系。 使用类型 特异性抗体，完成了Gs、Gi和Go的鉴定。 几种小细胞肺癌细胞系。 的生理相关性 这些蛋白质作为人类诱导的第二信息系统的调节剂， 通过对细胞生长的影响以及与其他膜的相互作用， 分子通过交联剂将被探索。 这些研究的意义在于自分泌作用的定义 对于胃泌素释放肽的实验室其他人需要进行研究， 关于生长激活途径是如何介导的。 这一点， 中间代谢途径的饲料可以允许设计合理的 治疗方法。

A) Gastrin Releasing Peptide Receptor: Model System. Gastrin-Releasing Peptide is a 27 amino acid peptide derived from a proGRP precursor, of which there are least three types which differ in relation to alternative splicing at the 3' end of the precursor in a location not involving the GRP portion of the molecule. To focus on the nature of a receptor for GRP, GH3 cells, a cloned rat pituitary cell line demonstrated enhanced phosphoinositide turnover in response to binding of bombesin. This process was partially sensitive to pertussis toxin and could be elicited by as low as 0.15 uM bombesin. On examining SCLC cultures, preliminary experiments suggest a small but reproducible tumor in phosphoinositide turnover after addition of bombesin to a cell line known to have receptors. Crosslinking agents have been used to confirm specific binding of labelled GRP to GH3 and 3T3 cells, and will be used in further attempts to characterize and perhaps purify the GRP receptor. B. Guanine Nucleotide Regulatory Protein in Lung Cancer. Using type specific antibodies, identification of Gs, Gi and Go was accomplished in several small cell lung cancer cell lines. The physiologic relevance of these proteins as regulators of human induced second message system will be explored, via effects on cell growth, and interactions with other membrane molecules by cross linking agents will be explored. The significance of these studies is that definition of an autocrine role for gastrin-releasing peptide by others in the lab needs to be pursued with respect to how the growth activated pathway is mediated. Points where this pathway feeds into intermediary metabolism could allow design of rational therapeutic approaches.