PHARMACOLOGICAL REGULATION OF THE PROSTACYCLIN RECEPTOR

前列环素（PGI 2）是一种血小板抑制剂、血管扩张剂类花生酸 血管组织对血栓形成和血管收缩剂的反应 刺激。 该项目旨在利用这一生物概况来解决 这种稳态受体的过度表达 配体可以调节体内对血管闭塞事件的反应。 最初，这个项目的目的是描述伴随的分子事件 PGI 2受体（IP 2 R）脱敏，使用表位的纯化 标记的受体、基于肽的抗体和串联质谱， 指导抗脱敏突变体的构建。 野生型 突变受体将在腺病毒构建体中递送到血管 细胞及其限制血小板-血管壁相互作用的有效性 将被探索。 这些实验将利用体外系统， 导致使用体内模型，包括建立的犬模型， 血栓形成和胚胎干细胞Ip 2 R受体敲除小鼠。 的 野生型和突变型受体的比较效力将是 评估。

Prostacyclin (PGI2) is a platelet inhibitory, vasodilator eicosanoid elaborated by vascular tissue in response to thrombotic and vasoconstrictor stimuli. This project aims to utilize this biological profile to address the hypothesis that overexpression of receptors for such homeostatic ligands might modulate the response to vascular occlusive events in vivo. Initially, this project aims to characterize the molecular events attendant to PGI2 receptor (IP2R) desensitization, using purification of an epitope tagged receptor, peptide-based antibodies and tandem mass spectrometry to direct the construction of desensitization resistant mutants. Wild type and mutant receptors will be delivered in adenoviral constructs to vascular cells and their effectiveness in limiting platelet-vessel wall interactions will be explored. These experiments will utilize in vitro systems and will lead to the use of in vivo models including an established canine model of thrombosis and an embryonic stem cell Ip2R receptor knock out mouse. The comparative efficacy of the wild type and mutant receptors will be assessed.