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Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs

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Summary

The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and plateletcyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioassayed as RCS on rabbit aorta strips, PGI2 in terms of its antiaggregatory activity on ADP-induced aggregation of human platelet-rich plasma.

All of the substances studied produced concentration-dependent inhibition of PGI2- and RCS-release. The IC50 [μM] in inhibition of RCS-formation was 0.019 for indomethacin, 0.070 for tiaprofenic acid but 44.9 for meclofenamate and 63.2 for diclofenac. The IC50 [μM] in inhibition of PGI2-release was 0.42 for diclofenac, 0.63 for indomethacin and 0.99 for tiaprofenic acid. The data suggest (1) high sensitivity of human platelet-cyclooxygenase against indomethacin and tiaprofenic acid, (2) different sequence of the substances studied in inhibiting arachidonic acid-induced TXA2- and PGI2-formation. The possible therapeutic value of selective inhibition of platelets and vascular cyclooxygenases in discussed.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität zu Köln, Gleueler Strasse 24, D-5000, Köln 41, Federal Republic of Germany

    K. Schrör, S. Sauerland, A. Kuhn & R. Rösen

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  1. K. Schrör
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  2. S. Sauerland
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  3. A. Kuhn
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  4. R. Rösen
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Schrör, K., Sauerland, S., Kuhn, A. et al. Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs. Naunyn-Schmiedeberg's Arch. Pharmacol. 313, 69–75 (1980). https://doi.org/10.1007/BF00505806

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  • DOI: https://doi.org/10.1007/BF00505806

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