PROSTACYCLIN AND THROMBOXANE-A2 IN OCULAR TISSUES

我们打算确定的生物合成的洋地黄素（PGs）和新的 发现血栓素和前列环素（PGI 2）的化合物， 虹膜、结膜、视网膜和透镜等组织。 花生四烯酸被代谢成三种主要化合物：（1）E和F的PG 型，现在已知参与炎症的介导;（2） PGI 2是一种有效的血管扩张剂、cAMP刺激剂和 血小板聚集;和（3）血栓素-A2（TxA 2），其是一种有效的 血管收缩剂和血栓形成剂。 这三者之间的相互作用 花生四烯酸在正常和病理状态下的代谢产物还没有 知道的 在这个建议中，我们特别感兴趣的是， 组织有能力在正常和病理中合成这些化合物， （炎症）状况。 此外，我们打算研究年龄的影响， 和种间差异。 另外我们 我想扩大我们的研究，开发特异性的酶抑制剂， 从花生四烯酸生物合成PGE 2和PGF 2 α，TxA 2和PGI 2。 这些研究将使我们能够了解生物合成的变化， 正常和病理性眼组织中的PGs、血栓素和PGI 2，以及 从而进一步了解这些化合物可能的功能作用。 事实上，这些非常具有生物活性的内源性物质已经 被证明是由某些眼组织生物合成的，这表明 这些药物在眼功能中的作用。

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.