Effects of thiazinamium chloride, promethazine and chlorpromazine on thromboxane B2 synthesis, phagocytosis and respiratory burst by rat alveolar macrophages.
The effects of three phenothiazines, promethazine, thiazinamium chloride and chlorpromazine, on macrophage function were investigated in rat alveolar macrophages. The study focused on thromboxane B2 (TxB2) synthesis, zymosan phagocytosis, and hexosemonophosphate (HMP) shunt activity in these phagocytes. TxB2 synthesis by resting macrophages was inhibited by thiazinamium chloride and promethazine in a dose-dependent manner. However, chlorpromazine was inhibitory only at 10(-3) M. Promethazine treatment of zymosan-activated macrophages led to a concomitant reduction in both phagocytosis and TxB2 synthesis. Thiazinamium chloride inhibited TxB2 synthesis but had no effect on the ingestion of zymosan particles. In contrast, chlorpromazine inhibited phagocytosis but not TxB2 synthesis except at 10(-3) M. The effects of these agents on the formation of TxB2 synthesis from exogenous arachidonic acid were also investigated. Under these conditions where indomethacin, a known cyclooxygenase inhibitor, was inhibitory, promethazine but not thiazinamium chloride inhibited TxB2 synthesis from exogenous arachidonic acid. Treatment of macrophages with promethazine and chlorpromazine but not thiazinamium chloride results in a reduction in the oxidative burst during phagocytosis. The results suggest that the phenothiazines used in this study differ from one another in their actions on macrophage function. Furthermore, the ability of thiazinamium chloride to selectively inhibit arachidonic acid metabolism may contribute to its bronchodilator/antiallergic activity.
D000818:Animals; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D009241:Ipratropium / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D011398:Promethazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D013929:Thromboxane B2; D011398:Promethazine; D009241:Ipratropium; D002746:Chlorpromazine; D007213:Indomethacin