Mechanisms of Leukotriene Biosynthesis and Physiological Action in Amphibians

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9318047 Herman Eicosanoids are biomedically important hormones. They have diverse actions including effects on blood clotting, inflammation, anaphylaxis, and cardiovascular and nervous system regulation in mammals. Eicosanoids include prostaglandins and leukotrienes and are synthesized from arachidonic acid, a polyunsaturated fatty acid found in cell membranes. When diets high in fish are consumed, membranes contain high quantities of eicosapentaenoic acid and the eicosanoids synthesized from this fatty acid have less biological activity. While much work has been done on the biochemistry and physiology of eicosanoids in mammals, much less is known of their roles in other animals. White blood cells in mammals produce leukotrienes, but red cells lack this capacity. However, bullfrog red blood cells synthesize leukotrienes, therefore, regulation of synthesis will be investigated. Frog membranes contain high levels of eicosapentaenoic acid which may affect synthesis. Leukotrienes may act by stimulating synthesis of prostaglandins, and this will be investigated using isolated bullfrog lung strips. Since antagonism of leukotriene effects is biomedically important, receptor antagonists will be tested in cannulated bullfrogs in vivo. Amphibian tissues are simpler than their mammalian counterparts, therefore, mechanisms and results will be easier to interpret. This research will provide insight into the evolution of these biomedically important compounds. ***