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. 1982 Apr;75(4):623–631. doi: 10.1111/j.1476-5381.1982.tb09183.x

Prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation of rabbit platelets

G P Lewis, I S Watts
PMCID: PMC2071527  PMID: 6802211

Abstract

1 A bioassay technique is described for simultaneously monitoring rabbit platelet aggregation with measurement of thromboxane A2 (TxA2) and prostaglandins released in response to collagen or arachidonic acid (AA).

2 Five imidazole derivatives were examined as inhibitors of thromboxane synthetase and compared with the effect of the cyclo-oxygenase inhibitor indomethacin; 1-(7-carboxyheptyl) imidazole was identified as the most potent and selective inhibitor of thromboxane synthetase and was used with indomethacin to investigate the relative contribution of the prostaglandin endoperoxides prostaglandin G2 (PGG2)/PGH2 and TxA2 in mediating platelet aggregation induced by collagen or AA.

3 Platelet aggregation induced by a low concentration of collagen was abolished by indomethacin and carboxyheptylimidazole whilst in response to a high concentration or collagen only partial inhibition of aggregation occurred.

4 The contribution of adenosine diphosphate (ADP) released from platelets during collagen or AA-induced aggregation was examined using the substrate/enzyme complex creatine phosphate/creatine phosphokinase (CP/CPK). The CP/CPK complex abolished aggregation induced by a low dose of collagen whilst aggregation to a high dose of collagen was only partially inhibited.

5 Aggregation induced by a high dose of collagen was abolished by a combination of CP/CPK with indomethacin or carboxyheptylimidazole.

6 AA-induced aggregation was abolished by indomethacin. Carboxyheptylimidazole abolished aggregation induced by a low dose of AA but inhibition was surmounted with increasing concentrations of AA in the absence of TxA2 formation.

7 PGH2-induced aggregation was unaffected by indomethacin and only partially inhibited by carboxyheptylimidazole. AA or PGH2-induced platelet aggregation was unaffected by CP/CPK.

8 In conclusion, aggregation of rabbit platelets induced by a low concentration of collagen was dependent on synergism between TxA2 and ADP whilst at high concentrations of collagen, sufficient TxA2 and ADP were released to induce aggregation independently of each other.

9 The small amounts of prostaglandin endoperoxides produced from endogenous arachidonate have apparently no direct pro-aggregatory role. However, the relatively large amount which can be produced by a high concentration of exogenous AA when TxA2 formation is prevented can cause aggregation of rabbit platelets.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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