MOLECULAR ANALYSIS OF MAMMALIAN BOMBESIN RECEPTOR

此前，我们克隆并鉴定了两种不同的药理作用 对胃泌素具有高亲和力的蛙皮素受体(GRP-R和NMB-R) 释放肽(GRP)或神经梅毒素B(NMB)。最近， 我们分离并鉴定了第三种截然不同的哺乳动物受体 从培养的人肺癌细胞中提取蛙皮素肽(BRS-3)，这 表达后被蛙皮素肽特异性激活的受体 在非洲爪哇的卵母细胞中。然而，更高浓度的多肽(更多 大于1微摩尔)才能重现地引起反应， 这表明高亲和力的蛙皮蛋白配体还没有被 已为BRS-3确定。受体激活导致血管紧张素转换酶升高 细胞内钙，推测是通过G-G-G样偶联 激活磷脂酶C-β1.BRS-3的异三聚体G蛋白 在人肺癌细胞和继发性肺癌细胞中选择性表达 精母细胞，但既不在胃肠道，也不在中枢，并映射到人类 染色体X受体嵌合体构建于GRP-R和NMB-R之间 映射负责高亲和力NMB结合和效应器的结构域 向跨膜片段5发送信号。

Previously, we cloned and characterized two pharmacologically distinct bombesin receptors (GRP-R and NMB-R) with high affinity for gastrin- releasing peptide (GRP) or neuromedin B (NMB), respectively. Recently, we isolated and characterized a third distinct mammalian receptor for bombesin peptides (BRS-3) from cultured human lung cancer cells, This receptor is specifically activated by bombesin peptides after expression in Xenopus oocytes. However, higher concentrations of peptide (greater than 1 micromole) are needed to reproducibly elicit the response, indicating that a high-affinity bombesin ligand has not as yet been determined for BRS-3. Receptor activation results in elevation of intracellular calcium, presumably coupling through a G-g-like hetertrimeric G-protein which activates phospholipase C-beta 1. BRS-3 is selectively expressed in human lung cancer cells and secondary spermatocytes, but neither in the GI tract nor CNS, and maps to human chromosome X. Receptor chimeras constructed between the GRP-R and NMB-R map the domain responsible for high-affinity NMB-binding and effector signalling to transmembrane segment 5.