Leukotriene Synthesis and Action in Amphibians

白三烯是哺乳动物用5-脂氧合酶/LTA4合成酶由花生四烯酸合成的重要的生物医学调节性化合物。然而，关于白三烯的结构和功能的信息在非哺乳动物脊椎动物中几乎完全缺乏。研究白三烯在变温脊椎动物中的合成和作用是很重要的。例如两栖动物，因为(a)它们的细胞膜含有其他可能调节白三烯合成的多不饱和脂肪酸(b)代谢和生理过程受环境温度的影响；(c)青蛙的组织比哺乳动物组织简单，可以作为白三烯作用的较不复杂的模型。该实验室先前的研究已经证明白三烯对空心牛蛙的低血压有生物学作用，并在离体牛蛙心脏和肺条的收缩性体外研究中证明了白三烯对低血压的生物学作用。本提案将探讨：1)心脏、肺和血管对白三烯合成的调节；2)环核苷酸和磷酸肌苷参与白三烯在心脏、肺和血管系统中的作用机制；3)利用放射受体测定和放射自显影技术表征白三烯与两栖动物心脏和肺膜受体的结合。这项研究将进一步深入了解这些重要调控化合物的进化过程

Leukotrienes are biomedically important regulatory compounds synthesized from arachidonic acid by 5-lipoxygenase/LTA4 synthase in mammals. However, information concerning the structures and functions of leukotrienes is almost completely lacking in non- mammalian vertebrates. It is important to examine leukotriene synthesis and action in poikilothermic vertebrates, such as amphibians because (a) their cell membranes contain other polyunsaturated fatty acids which may modulate leukotriene synthesis (b) metabolic and physiological processes are affected by environmental temperature and (c) frog tissues are simpler than their mammalian counterparts and can serve as less complex model for leukotriene action. Previous research by this laboratory has demonstrated biological effects of leukotrienes on hypotension in cannulated bullfrogs and in in vitro studies on contractility of isolated bullfrog heart and lung strips. This proposal will examine 1) regulation of leukotriene synthesis by heart, lung, and blood vessels 2) involvement of cyclic nucleotides and phosphoinositides in the mechanism of leukotriene action on the heart, lung, and vascular system and 3) characterization of leukotriene binding to amphibian heart and lung membrane receptors using radioreceptor assays and autoradiography. The proposed research will provide additional insight into the evolution of these important regulatory compounds.//