Inhibition of platelet thromboxane synthesis by 7-(1-imidazolyl) heptanoic acid: dissociation from inhibition of aggregation.

Abstract

Abstract The effects of 7-(1-imidazolyl)heptanoic acid (7-IHA), a thromboxane synthetase inhibitor, and indomethacin on platelet aggregation and immunoreactive thromboxane B2 (iTXB2) synthesis were studied in human platelet rich plasma. The ID50 for inhibition of arachidonic acid induced iTXB2 synthesis by 7-IHA was 1.9 μM but the ID50 for inhibition of platelet aggregation was estimated to be 1.35 mM. 7-IHA (0.5 mM) inhibited arachidonic acid induced iTXB2 synthesis to values less than that obtained in the presence of indomethacin (10 μM); but did not inhibit aggregation, while indomethacin completely inhibited platelet aggregation. 7-IHA had no effect on platelet fatty acid cyclooxygenase; did not promote synergism with ADP or arachidonic acid; arachidonic acid plus ADP or stable PGH2 analogs. We conclude: 1) that 7-IHA is a specific inhibitor of platelet thromboxane synthesis which at the same concentrations does not inhibit arachidonic acid induced platelet aggregation and 2) that inhibition of platelet TXA2 synthesis by thromboxane synthetase inhibitors may not necessarily inhibit arachidonic acid induced platelet aggregation.