Leukotriene Synthesis and Action in Amphibians

白三烯是哺乳动物体内由花生四烯酸通过5-脂氧合酶/LTA4合成酶合成的具有重要生物医学意义的化合物。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。研究变温脊椎动物(如两栖动物)中白三烯的合成和作用是很重要的，因为(A)它们的细胞膜含有可能调节白三烯合成的其他多不饱和脂肪酸(B)代谢和生理过程受环境温度的影响，(C)蛙类组织比它们的哺乳动物组织简单，可以作为白三烯作用的不太复杂的模型。该实验室之前的研究已经证明了白三烯对空心牛蛙低血压的生物学效应，以及对牛蛙离体心和肺条收缩能力的体外研究。这项建议将研究1)心、肺和血管对白三烯合成的调节，2)环核苷酸和磷脂酰肌醇参与白三烯对心、肺和血管系统的作用机制，以及3)利用放射受体分析和放射自显影术表征白三烯与两栖动物心和肺膜受体的结合。拟议的研究将为这些重要的调节性化合物的进化提供更多的洞察力。

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.//