Biophysical and Biochemical Studies on the Regulatory Mechanism of Fatty Acids on Blood Platelet Functions

脂肪酸对血小板功能调节机制的生物物理生化研究

基本信息

批准号：
63571020
负责人：
KITAGAWA Shuji
金额：
$ 1.28万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

cis-Polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid inhibit platelet aggregation induced by ADP and other agonists. They inhibited the aggregation due to the inhibition of agonist-induced increase in cytoplasmic Ca^<2+>. Therefore, we then observed the effects of the fatty acids on the levels of intracellular cyclic AMP which is known to be one of the substances to regulate intracellular Ca^<2+>. According to radioimmunoassay study, addition of these fatty acids increased cyclic AMP contents in the presence of theophylline corresponded with their inhibitory effects on aggregation. These fatty acids induced a 1.6 % - 1.8 times increase over basal concentration of cyclic AMP in the concentration ranges that fully inhibited aggregation. On the other hand, saturated fatty acid, stearic acid, affected neither aggregation nor cyclic AMP levels. cis-Polyunsaturated fatty acids did not affect the production of inositol- 1,4,5-trisphosphate (IP_3) which is suggested to trigger Ca^<2+> release from intracellular pools. The possibility was also denied that these unsaturated fatty acids inhibit platelet functions by inhibiting arachidonate metabolism. Adenylate cyclase, which is responsible for the synthesis of cyclic AMP, is believed to be modulated by the lipid environment of the membrane. Fluorescence analysis with diphenylhexatriene and its trimethylammonium derivative showed that polyunsaturated fatty acids commonly increased membrane fluidity in wide depths of the membrane in the concentration ranges in which these fatty acids increased cyclic AMP concentration and inhibited platelet aggregation. From these results it is concluded that polyunsaturated: fatty acids inhibit platelet aggregatio due to stimulation of adenylate cyclase which is mediated by membrane betturbation.

顺式 - 多饱和脂肪酸，例如亚油酸和α-亚麻酸，抑制ADP和其他激动剂诱导的血小板聚集。由于抑制激动剂诱导的细胞质Ca^<2+>，它们抑制了聚集。因此，我们随后观察到脂肪酸对细胞内循环AMP水平的影响，这是调节细胞内Ca^<2+>的物质之一。根据放射免疫测定研究，在茶碱存在下，这些脂肪酸的添加增加了环状AMP含量，与它们对聚集的抑制作用相对应。这些脂肪酸在浓度范围内完全抑制聚集的浓度范围内诱导了1.6％-1.8倍。另一方面，饱和脂肪酸，硬脂酸，既不影响聚集也不影响环状AMP水平。 CIS-饱和脂肪酸不会影响肌醇-1,4,5-三磷酸（IP_3）的产生，这建议触发Ca^<2+>从细胞内池释放。可能性也否认，这些不饱和脂肪酸通过抑制蛛网膜代谢抑制血小板的功能。腺苷酸环化酶（负责合成环状AMP）被认为是由膜的脂质环境调节的。用二苯基甲基苯二他烯及其三甲基铵衍生物分析表明，多不饱和脂肪酸通常会在膜深度上增加膜的流动性，其中这些脂肪酸会增加环状AMP浓度并抑制血小板的聚集。从这些结果得出的结论是，多不饱和：脂肪酸由于刺激腺苷酸环化酶而抑制血小板聚集，这是由膜脑扰动介导的。