Role Of Thromboxane (TXA2 ) And Adp In Collagen-Induced Platelet Aggregation

Abstract

TXA2 and prostaglandins (PGs) released during collagen- induced aggregation of rabbit platelets were bioassayed on rabbit aorta (RA) and rat stomach strip (RSS) respectively in a cascade system. Platelet aggregation was monitored simultaneously. The technique was used to examine modulation of aggregation and release of TXA2 and PGs by inhibitors of TX synthetase (l-(7-carboxyheptyl)imidazole) (CHI) and cyclo-oxygenase (CO) (indomethacin, Indo).At low dose collagen (5-10 μg/ml) Indo and CHI completely inhibited platelet aggregation in a dose-related fashion. In contrast, at high dose collagen (50 μg/ml) these compounds gave only a partial (30-40%) inhibition of aggregation, at a dose which abolished CO and TX synthetase activity.The substrate/enzyme combination of creatine phosphate (CP) 5mM and creatine phosphokinase (CPK) 10 units/ml (which converts ADP to ATP) completely inhibited aggregation induced by low dose collagen but only partially inhibited (20%) that induced by high dose collagen. Neither CP nor CPK alone was effective.A mixture of both CP/CPK and CHI abolished the platelet aggregation induced by a high dose of collagen.These studies support the concept that collagen-induced aggregation is dependent on at least two mechanisms.Firstly, at low collagen concentration, subthreshold levels of released ADP and TXA2 act synergistically in inducing platelet aggregation since either CP/CPK or CHI abolished aggregation. Secondly, at high collagen concentration, sufficient ADP and TXA2 are released to induce aggregation independently of each other, since CP/CPK or CHI produced only partial inhibition of aggregation, whilst in combination aggregation was abolished. Furthermore, the results suggest that endoperoxides play no significant role in collagen-induced platelet aggregation.