The role of serotonin in ischemic cellular damage and the infarct size-reducing effect of sarpogrelate, a 5-hydroxytryptamine-2 receptor blocker, in rabbit hearts

Abstract

Sarpogrelate reduces the myocardial infarct size by inhibiting the serotonin release followed by enhancement of PKC-epsilon translocation and opening of the mitochondrial KATP channel in ischemic myocytes.

Persistent Insulin-Sensitizing Effects of Sarpogrelate Hydrochloride, a Serotonin 2A Receptor Antagonist, in Patients With Peripheral Arterial Disease

“…Various favorable cardiovascular pleiotropic actions of sarpogrelate have been reported. [1][2][3][4][5] A recent preliminary study by Yamakawa et al 14 showed a chronic increase in circulatory adiponectin and reduced HOMA-R in a small number of patients with treated diabetes mellitus (n=8) following sarpogrelate administration. Considering the wide range of actions of adiponectin on ASCDs, [13][14][15][16][17][18] sarpogrelate might have a beneficial effect on risk factor control and secondary prevention of ASCDs.…”

Sarpogrelate, a 5-HT2 Receptor Blocker, may Have a Preconditioning-Like Effect in Patients With Coronary Artery Disease

“…Recently, we reported the infarct-size reducing effect of sarpogrelate in rabbit hearts without collateral flow. 10 That effect was completely blocked by a selective PKC inhibitor, chelerythrine, and a mitochondrial KATP channel blocker, 5-hydroxydecanoate, suggesting that the mechanism was related to translocation of PKC followed by opening of a mitochondrial KATP channel, which is the same mechanism as IPC. 10 In addition, it has been shown that serotonin (5HT) is released from cardiac cells, such as from platelets in the vascular beds, mast cells and sympathetic nerve endings, within the area at risk during ischemia.…”

“…10 That effect was completely blocked by a selective PKC inhibitor, chelerythrine, and a mitochondrial KATP channel blocker, 5-hydroxydecanoate, suggesting that the mechanism was related to translocation of PKC followed by opening of a mitochondrial KATP channel, which is the same mechanism as IPC. 10 In addition, it has been shown that serotonin (5HT) is released from cardiac cells, such as from platelets in the vascular beds, mast cells and sympathetic nerve endings, within the area at risk during ischemia. 10 The increase in myocardial interstitial serotonin induces the release of a large amount of serotonin from aggregated platelets via their 5-HT2A receptors.…”

“…9 Recently, we showed that sarpogrelate reduced the size of the myocardial infarct in rabbit hearts without collateral circulation, and that the same mechanism as ischemic preconditioning (IPC), from the translocation of protein kinase C (PKC) to the opening of mitochondrial KATP channels, plays an important role in the protective effect. 10 We also previously reported that nicorandil, a hybrid nitrate with a KATP channel opening effect, which is currently used clinically as an anti-anginal and cardioprotective drug, 11,12 has a pharmacological preconditioning (PC) effect during percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). 13 Therefore, the aim of the present study was to clarify the anti-ischemic effect of sarpogrelate and its mechanism using a similar PCI model in patients with CAD.…”

Immuno-Thrombotic Effects of Platelet Serotonin

“…5-HT levels are drastically increased during myocardial ischemia, and blockade of the 5-HT 2 receptor improves the outcome after myocardial infarction in different mouse models [52,53].…”