Mechanisms of Leukotriene Biosynthesis and Physiological Action in Amphibians

[9318047]类二十烷酸是生物医学上重要的激素。它们具有多种作用，包括对哺乳动物的凝血、炎症、过敏反应以及心血管和神经系统调节的影响。类二十烷酸包括前列腺素和白三烯，由花生四烯酸合成，花生四烯酸是细胞膜中发现的一种多不饱和脂肪酸。当食用富含鱼类的饲料时，细胞膜中含有大量的二十碳五烯酸，而由这种脂肪酸合成的类二十碳五烯酸的生物活性较低。虽然对哺乳动物中类二十烷酸的生物化学和生理学已经做了很多工作，但对它们在其他动物中的作用所知甚少。哺乳动物的白细胞产生白三烯，但红细胞缺乏这种能力。然而，牛蛙红细胞合成白三烯，因此，合成的调控将被研究。蛙膜含有高水平的二十碳五烯酸，这可能会影响合成。白三烯可能通过刺激前列腺素的合成而起作用，这将用分离的牛蛙肺条进行研究。由于白三烯的拮抗作用具有重要的生物医学意义，受体拮抗剂将在空心牛蛙体内进行试验。两栖动物的组织比哺乳动物简单，因此，机制和结果将更容易解释。这项研究将为这些生物医学上重要的化合物的进化提供深入的见解。＊＊＊

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. ***