Abstract
Aim:
In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1) had neuroprotective effects in a rodent ischemic model. In the present study we aimed to investigate the inhibitory effect of PGA 1 on platelet function.
Method:
The rate of aggregation of human platelets was measured by using turbidimetry. The rate of adhesion of platelets to cultured endothelial cells was determined by using [3H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB2, a stable metabolite of TXA2, were determined by radioimmunoassay. Alternations in platelet morphology were observed using an electron microscope, and the intraplatelet free calcium concentrations were measured with Fluo-3/AM FCM assay.
Results:
PGA1 significantly inhibited thrombin-, collagen- and ADP-induced aggregation and adhesion of platelets. The morphological changes of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release of 5-hydroxytyptamine from dense granules and the synthesis of TXA2.
Conclusion:
PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA2 synthesis.
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Project supported by grants from the Department of Education of Jiangsu Province (03KJB310123); the Natural Science Foundation of Jiangsu Provinc (BK2004037); the National Natural Science Foundation of China (No 30470587); and Otsuka Pharmaceutical Co, Japan.
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Zhu, Y., Gu, Zl., Liang, Zq. et al. Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA2 production and platelet activation. Acta Pharmacol Sin 27, 549–554 (2006). https://doi.org/10.1111/j.1745-7254.2006.00311.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00311.x
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