ROLE OF PROSTAGLANDIN, THROMBOXANE AND RELATED AUTACOIDS

前列腺素、血栓烷和相关自体激素的作用

• 批准号: 3257152
• 负责人: PRASAD S KULKARNI
• 金额: $ 18.44万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3257152
• 关键词: Macaca; Macaca mulatta; antiinflammatory agents; arachidonate; autoradiography; bioassay; blood aqueous barrier; bradykinin; chromatography; disease /disorder model; drug metabolism; eicosanoids; enzyme inhibitors; eye infections; eye pharmacology; fatty acid biosynthesis; guinea pigs; histamine; human tissue; inflammation; iris; laboratory rabbit; laboratory rat; leukotrienes; lipoxygenase; neutrophil; prostacyclins; prostaglandin E; prostaglandin F; prostaglandin endoperoxide synthase; radioimmunoassay; scintillation counter; spectrometry; steroids; thromboxanes; uveitis

We have thus far determined the capacities of different ocular tissues such as conjunctiva, anterior uvea and cornea of various species (including monkey and human) to synthesize cyclooxygenase products: prostaglandins (PGs) PGE2, PGF2alpha, PGI2, PGD2 and thromboxane A2, and lipoxygenase products: monohydroxy acids and leukotrienes, from arachidonic acid (AA). In this proposal, we plan to study the roles these products play in the three phases (initiation, maintenance and termination) of ocular inflammation, especially the cellular inflammatory response. Their interaction with each other and other putative mediators such as histamine, bradykinin and chemotactic formylmethionyl polypeptide will be studied as well. In order to investigate the role of AA metabolites as either mediators or modulators, we will study the following using rabbits, cats and rats: 1) correlate the endogenous synthesis and release of PGs, thromboxane and leukotrienes with polymorphonuclear leukocytes (PMNs) infiltration of ocular fluids and tissues and breakdown of the blood-aqueous barrier during three phases of ocular inflammation. Three types of inflammation models will be used: a) paracentesis (no cellular response), b) endotoxin-induced uveitis (all inflammatory responses present) and c) corneal deepithelialization. 2) determine whether or not exogenous PGs and leukotrienes produce one or all inflammatory responses, administered alone or in combination with other autacoids to the normal eye. 3) determine whether or not drugs (steroidal and nonsteroidal), which interfere with AA metabolism at various enzymatic steps, affect one or all inflammatory responses in the three experimentally induced inflammation models outlined above. These studies will also be correlated with measuring the PMN count, leukotriene content and PG levels in tear fluids of volunteers with contact lens allergies. These studies will help in understanding the mechanism of mediators of ocular inflammation and development of new anti- inflammatory drugs.

到目前为止，我们已经确定了不同眼球的容量 结膜、前葡萄膜、角膜等各种组织 要合成的物种(包括猴子和人类) 环氧合酶产物：前列腺素(PGs)PGE2、PGF2pha、 PGI2、PGD2和血栓素A2以及脂氧合酶产物： 单羟基酸和白三烯，来自花生四烯酸(AA)。 在这项提案中，我们计划研究这些产品在 三个阶段(启动、维护和终止) 眼部炎症，尤其是细胞性炎症 回应。他们彼此之间的互动以及其他假定的 组胺、缓激肽和趋化因子等介质 甲酰甲硫基多肽也将被研究。 为了研究AA代谢物作为 调解器或调制器，我们将研究以下使用 兔子、猫和老鼠： 1)内源性PGs的合成和释放， 血栓素和白三烯与多形核白细胞 (PMN)眼液和组织的渗透和分解 眼部三个阶段的血-房水屏障 发炎。将使用三种类型的炎症模型： A)穿刺术(无细胞反应)，b)内毒素性葡萄膜炎 (所有炎症反应都存在)和c)角膜 深度本土化。 2)确定外源性前列腺素和白三烯是否 产生一种或所有炎症反应，单独给药或 与其他耳石相结合，形成正常的眼球。 3)确定药物(类固醇和非类固醇)， 它们在不同的酶促步骤中干扰AA的代谢， 影响三种炎症反应中的一种或全部 上述实验诱导的炎症模型。 这些研究还将与测量PMN相关 泪液细胞计数、白三烯含量和PG水平 对隐形眼镜过敏的志愿者。 这些研究将有助于了解其发病机制。 眼部炎症介质与新型抗炎症药物的研究进展 发炎药。