PEPTIDE PROBES OF THE 5HT1A RECEPTOR G PROTEIN INTERFACE

5-羟色胺受体参与人类健康的许多方面， 疾病。我们工作的长期目标是研究分子 这些受体的药理学，特别强调相互作用 在5-羟色胺受体和一个重要的细胞信号转导之间 系统，G蛋白系统。在本项目中，我们提出了研究 与一种被称为5HT1a受体的人类5-羟色胺受体有关。这 受体属于一个大的受体超家族，包括其他 重要的模型受体，如肾上腺素能和M胆碱能 感受器。基于这些模型受体的已知特征， 代表5HT1a生物重要区域的特异性多肽 受体的合成将采用固相法。这些多肽将 然后针对膜结合和溶解的人5HT1a 受体。对受体-G蛋白相互作用的干扰 通过激动剂抑制试验和通过测量对 第二信使环磷酸腺苷。从这些研究中获得的信息将 有助于了解该受体的生物学和结构 系统，并可能有助于开发新的治疗药物。 此外，结果可能会以更一般的方式对模型做出贡献 受体超家族的系统。

Serotonin receptors are involved in many aspects of human health and disease. The long-term goals of our work are to study the molecular pharmacology of these receptors, particularly emphasizing the interactions between serotonin receptors and a significant cellular signal transducing system, the G protein system. In the present project, we propose studies with a type of human serotonin receptor known as the 5HT1a receptor. This receptor belongs to a large superfamily of receptors which includes other important model receptors such as adrenergic and muscarinic cholinergic receptors. Based upon known characteristics of these model receptors, specific peptides representing biologically important regions of the 5HT1a receptor will be synthesized by solid phase methods. These peptides will then be directed against membrane-bound as well as solubilized human 5HT1a receptor. Interference with receptor-G protein interactions will be measured by agonist inhibition assays and by measuring effects on the second messenger cyclic AMP. Information gained from these studies will contribute to understanding the biology and structure of this receptor system, and may contribute to development of novel therapeutic drugs. Additionally, results may contribute in a more general manner to the model systems of the superfamily of receptors.