Studies on the inhibitory mechanism of MATS,a garlic oil component, to the thromboxane synthesis by platelets.

大蒜（Allium sativum L.）研究了其缓蚀机理。MATS抑制血小板血栓素A_2（TXA_2）的合成，其抑制方式与大多数已知的特异性抑制剂（如阿司匹林用于环氧合酶（考克斯），七叶皂甙用于脂氧合酶（LPX），OKY-046用于血栓烷合酶（TXS）。MATS抑制考克斯和LPX，但TXS在浓度低于10 μ <-4>M时抑制。MATS被判定为抑制前列腺素内过氧化物合酶（PGH合酶），然而，抑制仅限于其活性之一，过氧化物酶活性的方向。考克斯活性是这种双功能酶的另一种活性，已发现其被阿司匹林特异性抑制，但似乎不受MATS的影响，因为花生四烯酸以与对照相似的代谢率被消耗。尽管MATS与PGH合酶之间的详细相互作用尚未得到证实，但MATS可以通过其烷基硫醚结构阻止底物（PGG_2）的还原。MATS对主动脉血管壁内皮细胞产生PGI_2也有抑制作用。这些结果使我们怀疑MATS是否具有抗血栓作用。然后，我们将使用血栓形成的动物模型来研究MATS的体内效果。

A potent platelet aggregation inhibitor, methyl allyl trisulfide (MATS) found in the steam distillled oil components from garlic (Allium sativum L.) was studied to reveal its inhibition mechanism. MATS suppressed synthesis of thromboxane A_2 (TXA_2) in platelets, and showed quite different mode of inhibition from the most of all known specific inhibitors, e.g., aspirin for cyclooxygenase (COX) , esculetin for lipoxygenase (LPX) and OKY-046 for thrombaxane synthase (TXS). MATS inhibited both COX and LPX,but TXS at the concentration lower 10^<-4>M.MATS was judged to inactivate prostaglandin endoperoxide synthase (PGH synthase) , however, the inhibition was confined to the direction toward one of its activities, peroxidase activity. COX activity the another activity of this bifunctional enzyme, which has been found to be inhibited specifically by aspirin, seemed to be unaffected by MATS,since arachidonic acid was consumed with the metabolic rate similar to the control. Although, the detailed interaction between MATS and PGH synthase is not demonstrated yet, MATS would prevent the reduction of a substrate (PGG_2) through its alkyl sulfides structure. Against PGI_2 generation by the endothelial cells of aortic vessel walls, MATS also affected to reduce its levels. These results made us suspicious whether MATS acts practically antithrombotic. Then, we are about to investigate in vivo effect of MATS using an animal model of thrombosis.