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Figure 4 Role of serotonin in ischemia and reperfusion and the possible mechanism of the infarct size-reducing effect by sarpogrelate. Serotonin (5-hydroxytryptamine [5-HT]) is released from cardiac tissues within the area at risk, such as platelets in the vascular beds, mast cells, and sympathetic nerve endings, in ischemia and reperfusion. The increase in myocardial interstitial serotonin induces the release of a large amount of serotonin from platelet cytoplasm and platelet aggregation via 5-HT2A receptor on the cell membrane of platelets (#), and the myocardial interstitial serotonin is further increased. Note the presence of a vicious cycle among the released serotonin, 5-HT2A receptors, on the cell membrane of platelets and rich serotonin in platelet cytoplasm. Sarpogrelate, 5-HT2 receptor blocker, inhibits the binding between released serotonin and 5-HT2A receptors on the cell membrane of platelets and blocks the increase in interstitial serotonin by breaking the vicious circle. Translocation of protein kinase C (PKC)- from the cytosolic to the membrane fraction followed by opening of the mitochondrial adenosine triphosphate sensitive potassium channel is an intrinsic protective mechanism of cardiomyocytes against ischemic damage. The released serotonin during ischemia inhibits the translocation of PKC- (*). Sarpogrelate further enhances translocation of PKC- followed by opening of the mitochondrial adenosine triphosphate sensitive potassium channel and reduces infarct size via inhibition of serotonin release.
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