CONFERENCE ON EICOSANOID LIPID MEDIATORS

描述：（改编自申请人的摘要）类二十烷酸包括 花生四烯酸的前列腺素类、白三烯和环氧合酶代谢物。的 用非甾体抗前列腺素类药物调节前列腺素类合成 炎性药物和较新的环氧合酶-2（考克斯-2）抑制剂（例如， Celebra和Vioxx）和白三烯对白三烯作用的抑制 受体拮抗剂（例如Singular）在以下方面具有重要的临床后果： 治疗各种慢性疾病。目前，两大问题 前列腺素区域的问题是：1）为什么有两种考克斯同工酶，2）如何 这些同工酶在同一细胞中共同表达时独立发挥作用？ 对这些主题的研究集中在定义考克斯-1和-2如何耦合 在生物化学上与上游磷脂酶A2和下游前列腺素H2 （PGH2）代谢酶和前列腺素受体的不同 参与考克斯亚型的作用。联合国系统内尚未解决的主要问题 白三烯领域包括确定这些产品在宿主防御中的作用 反应，白三烯生物合成酶的结构生物学， 白细胞三烯介体作用的生物化学基础。 长期 这些研究的结果可能会扩大现有的使用 环氧化酶 和 脂肪氧化酶 抑制剂和 白三烯 受体 拮抗剂和前列腺素受体拮抗剂的发展。 的 环氧酶区不发达。环氧合酶代谢物包括 形成的环氧、单羟基和二羟基多不饱和脂肪酸 通过P450的作用。这些化合物可能在调节 血压和 局部炎症反应，和 因此，提供 潜在的重要治疗靶点。 环氧合酶的关键问题 该领域涉及定义与环氧酶代谢产物形成相关的P450 并定义了具有生物活性的特定环氧合酶代谢物， 重要性汇集研究广泛主题的调查人员 在eicosanoid领域将导致更全面的了解 调节这些脂质的生物合成和作用机制 调解员 重要的是，Keystone研讨会的形式提供了一个开放的， 研究生和博士后研究员互动的适宜环境 与类花生酸领域的资深研究人员合作

DESCRIPTION: (Adapted from Applicant's Abstract) Eicosanoids include the prostanoid, leukotriene and epoxygenase metabolites of arachidonic acid. The pharmacological regulation of prostanoid synthesis with nonsteroidal anti- inflammatory drugs and the newer cyclooxygenase-2 (COX-2)-inhibitors (e.g. Celebra and Vioxx) and the inhibition of leukotriene actions with leukotriene receptor antagonists (e.g. Singular) have important clinical consequences in the treatment of various chronic diseases. Currently, the two major questions in the prostanoid area are: 1) why are there two COX isozymes, and 2) how do these isozymes operate independently when co-expressed in the same cell? Research on these topics focuses on defining how COX-1 and -2 couple biochemically to upstream phospholipase A2 and downstream prostaglandin H2 (PGH2) metabolizing enzymes and on how different prostanoid receptors are involved in the actions of the COX isoforms. Major unresolved issues in the leukotriene area include defining the role of these products in host defense responses, the structural biology of leukotriene biosynthetic enzymes, and the biochemical bases for the mediator actions of leukotrienes. The long-term outcome of these studies is likely to extend the usage of available cyclooxygenase and lipoxygenase inhibitors and leukotriene receptor antagonists and the development of prostanoid receptor antagonists. The epoxygenase area is not as well developed. Epoxygenase metabolites include epoxy, monohydroxy, and dihydroxy polyunsaturated fatty acids that are formed via the actions of P450s. These compounds may play key roles in regulating blood pressure and in local inflammatory responses, and thus, offer potentially important therapeutic targets. Key questions in the epoxygenase field involve defining the P450s relevant to epoxygenase metabolite formation and defining the specific epoxygenase metabolites that are of biological importance. Bringing together investigators studying a broad range of topics in the eicosanoid area will lead to a more comprehensive understanding of the regulation of the biosynthesis and mechanisms of actions of these lipid mediators. Importantly, the Keystone Symposium format provides an open, congenial setting for graduate students and postdoctoral fellows to interact with senior researchers in the eicosanoid area.