Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA(2) production and platelet activation

Acta Pharmacol Sin. 2006 May;27(5):549-54. doi: 10.1111/j.1745-7254.2006.00311.x.

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 PGA1 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 [(3)H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB(2), a stable metabolite of TXA(2), were determined by radioimmuno-assay. 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 TXA(2).

Conclusion: PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA(2) synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / antagonists & inhibitors
  • Blood Platelets / drug effects
  • Calcium / blood*
  • Collagen / antagonists & inhibitors
  • Humans
  • Platelet Adhesiveness / drug effects*
  • Platelet Aggregation / drug effects*
  • Prostaglandins A / pharmacology*
  • Serotonin / blood
  • Thrombin / antagonists & inhibitors
  • Thromboxane A2 / biosynthesis*

Substances

  • Prostaglandins A
  • Serotonin
  • Thromboxane A2
  • Adenosine Diphosphate
  • Collagen
  • Thrombin
  • Calcium
  • prostaglandin A1