Selective inhibition of thromboxane biosynthesis in human blood mononuclear cells and the effects of mitogen-stimulated lymphocyte proliferation.
1. The effects of six imidazole compounds were examined on thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) production and mitogen-stimulated lymphocyte transformation in human blood mononuclear cells. 2. UK 37248 (4-(2-[IH-imidazol-l-yl]ethoxy)benzoic acid), imidazole and 1-methylimidazole selectively inhibited TxB2 synthesis in a dose-related manner, with corresponding increases in PGE2 production. 3. Clotrimazole, benzimidazole and 2-methylimidazole preferentially inhibited TxB synthesis but had little effect on PGE2 production. 4. Clotrimazole and benzimidazole inhibited proliferative responses of the lymphocytes, but UK 37248 and 1-methylimidazole did not affect transformation at concentrations which inhibited TxB2 synthesis to a similar level (over 90%). 5. The results do not support involvement of endogenous TxB2 in the process of lymphocyte mitogenesis or in the mechanism of the suppressive effects of some TxB2 synthetase inhibitors.
D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism
D007093:Imidazoles; D008934:Mitogens; D011458:Prostaglandins E; D013931:Thromboxanes; D013929:Thromboxane B2; D013936:Thymidine