MOLECULAR CHARACTERIZATION OF THE GALANIN RECEPTOR

甘丙肽是一种广泛分布于中枢和脑内的多肽。 周围神经系统。在胰腺中，甘丙素存在于 交感神经末梢环绕朗格汉斯胰岛，是 交感神经刺激时胰岛素分泌的主要抑制物 以及某些系统性的压力。尽管这些对胰岛素有很大的影响 分泌，甘丙肽受体阻断对II型糖尿病的影响 由于缺乏合适的甘丙素受体而未被研究 拦截者。作为确定结构要求的前奏 甘丙肽受体的配基结合域，这项研究概述于 这项提议的目的是为了阐明 甘丙肽受体、甘丙肽受体亚型的分布 与受体相关的第二信使系统的测定 子类型。通过实现这些目标而获得的新信息可以 然后用来确定配体结合的分子要求 并设计甘丙肽受体拮抗剂，以允许测试 甘丙素可能在不利的胰岛素中起作用的假说 II型糖尿病患者的分泌与胰岛素需求平衡。

Galanin is a peptide which is widely distributed in the central and peripheral nervous systems. In the pancreas, galanin is present in the sympathetic nerve terminals surrounding the islets of Langerhans and is a major inhibitor of insulin secretion during sympathetic nerve stimulation and certain systemic stresses. Despite these potent effects on insulin secretion, the effect of galanin receptor blockade in type II diabetes has not been investigated because of the lack of suitable galanin receptor blockers. As a prelude to determining the structural requirements of the ligand binding domain of the galanin receptor, the research outlined in this proposal is aimed at elucidating the molecular structure of the galanin receptor, the distribution of galanin receptor subtypes and the determination of the second messenger systems associated with the receptor sub types. The new information gained from achievement of these aims may then be used to determine the molecular requirements for ligand binding and to design galanin receptor antagonists to allow testing of the hypothesis that galanin may play a role in the unfavorable insulin secretion to insulin requirement balance in type II diabetes.