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.//
