Abstract
The effects of variety of drugs on metabolic burst and phospholipase A
2 in polymorphonuclear leukocytes (PMNs) were investigated. The stimulation of PMNs by n-formyl-methionyl-leucyl-phenylalanine (FMLP) causes arachidonic acid (AA) to be released in the cells concomitantly with the generation of superoxide anion. These variables were effectively diminished with some clinically employed drugs including chlorpromazine, trifluoperazine, azelastine, clemastine and mepacrine at the lower concentration of 20 μM. In contrast, indomethacin and procaine were ineffective even at the higher concentration of 100 μM. Subcellular fractionation of PMNs revealed that phospholipase A
2 activity was located both in the plasma membrane-rich fraction as well as the granule-microsome-rich fraction, and the potency of inhibition of membrane-bound phospholipase A
2 by the above mentioned drugs was: indomethacin (IC50=3 μM)<chlorpromazine<azelastine and clemastine (IC50>100 μM). The low potency of antipsychotropic drugs and antihistaminic drugs in inhibiting the fractionated phospholipase A
2 contrast with the high efficiency with which they inhibit the superoxide generation and the AA release from stimulated PMNs. The AA relaeses from the PMNs stimulated by FMLP or calcium ionophore (A23187) were almost equally diminished by various drugs at the lower concentration. From these obsevations, it appeared likely that these drugs might inhibit the metabolic stimulations of PMNs at the sites of the Ca
2+-dependent activation processes of the enzymes responsible for the AA release and the superoxide generation.
