PROSTACYCLIN AND THROMBOXANE-A2 IN OCULAR TISSUES

眼组织中的前列环素和血栓烷-A2

• 批准号: 3257150
• 负责人: PRASAD S KULKARNI
• 金额: $ 21.93万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-11-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3257150
• 关键词: antiinflammatory agents; arachidonate; chromatography; conjunctiva; cornea; cyclic AMP; eicosanoid metabolism; eye infections; eye pharmacology; fatty acid biosynthesis; human tissue; inflammation; lens; neutrophil; prostacyclins; prostaglandin E; prostaglandin F; radiotracer; retina; thromboxanes

We intend to determine the biosynthesis of prostaglandins (PGs) and the newly discovered compounds thromboxanes and prostacyclin (PGI2) in different ocular tissues like iris, conjunctiva, retina and lens from different species. Arachidonic acid is metabolized into three major compounds: (1) PGs of E and F type, which are now known to be involved in the mediation of inflammation; (2) PGI2, which is a potent vasodilator, stimulator of cAMP and an inhibitor of platelet aggregation; and (3) thromboxane-A2 (TxA2) which is a potent vasoconstrictor and thrombus forming agent. The interaction between these three arachidonic acid metabolites in normal and pathological conditions is not yet known. In this proposal we are particularly interested in whether the ocular tissues have an ability to synthesize these compounds in normal and pathological (inflammation) conditions. Also, we intend to study the influence of the age and species difference on this arachidonic acid metabolism. In addition, we want to extend our study in developing specific inhibitors of the enzymes which biosynthesize PGE2 and PGF2alpha, TxA2 and PGI2 from arachidonic acid. These studies will enable us to understand the changes in the biosynthesis of PGs, thromboxane and PGI2 in the normal and pathological ocular tissues, and therefore further understand the possible functional role of these compounds. The fact that these very biologically active endogenous substances have already been shown to be biosynthesized by certain ocular tissues indicates a possible role for these agents in ocular function.

我们打算确定前列腺素(PGs)的生物合成和新的 在不同眼部发现血栓素和前列环素(PGI2)化合物 来自不同物种的虹膜、结膜、视网膜和晶状体等组织。 花生四烯酸被代谢成三种主要化合物：(1)E和F的PGs 类型，现在已知参与了炎症的调节；(2) 前列腺素I2是一种强有力的血管扩张剂、cAMP刺激剂和 血小板聚集；和(3)血栓素A2(TXA2)，这是一种有效的 血管紧张剂和血栓形成剂。这三者之间的相互作用 花生四烯酸在正常和病理条件下的代谢物还不是 为人所知。在这项建议中，我们特别感兴趣的是眼睛是否 正常组织和病理组织都有合成这些化合物的能力。 (发炎)情况。此外，我们还打算研究年龄的影响 以及物种对花生四烯酸代谢的影响。此外，我们 我想扩大我们在开发特定的酶抑制剂方面的研究 以花生四烯酸为原料生物合成前列腺素E_2和前列腺素F_2α、血栓素A_2和前列环素。 这些研究将使我们能够了解生物合成的变化 正常眼组织和病理眼组织中PGS、TXX和PGI2的表达； 因此，进一步了解这些化合物可能的功能作用。 这些非常具有生物活性的内源物质已经 已经被证明是由某些眼睛组织生物合成的，这表明 这些药物在眼功能中的作用。