BIOLOGY OF ENDOTHELIN

该项目的目的是研究内皮素(ET)的生物学作用。 包括ET多肽及其受体的系统。具体来说， 该项目将检验这样一种假设，即每一种ET受体 Eta和EtB亚型是由Et配体唯一调节的，这 调节不同于通常的配体-受体相互作用。 因此，ET对ETA亚型的影响不大。相比之下，ET 上调ETB子类型。每种受体亚型依次调节 ET多肽本身的产生，从而使ETA发挥负作用 反馈以减少ET产生，而正反馈以增加 ET的产生是通过ETB受体亚型发生的。ETB受体 亚型还可能通过一氧化氮(NO)和 前列环素(PGI2)。ET激活的功能后果将是 然后由每个不同功能的贡献来确定 ETA介导血管收缩和ETB介导血管收缩的受体系统 血管收缩或血管扩张。这些项目还将审查一个 该系统的生理调节器，肾上腺素能神经系统，如 以及一种病理生理调节剂环孢素。

The projects aim is to study the biological role of the endothelin (Et) system which includes the Et peptide and its receptors. Specifically, the project will examine the hypothesis that each of the Et receptor subtypes, EtA and EtB, is uniquely modulated by the Et ligand and this modulation is distinct from the usual ligand-receptor interactions. Thus, Et has little effect on the EtA subtype. By contrast, Et upregulates the EtB subtype. Each receptor subtype, in turn, modulates production of the Et peptide itself, such that EtA exerts a negative feedback to decrease Et production while a positive feedback to increase Et production occurs through the EtB receptor subtype. The EtB receptor subtype may also suppress Et production through nitric oxide (NO) and prostacyclin (PGI2). The functional consequence of Et activation will then be determined by the contribution of the distinct function of each receptor system whereby EtA mediates vasoconstriction and EtB mediates vasoconstriction or vasodilation. The projects will also examine a physiologic modulator of this system, the adrenergic nervous system, as well as a pathophysiologic modulator, cyclosporine.