Possible involvement of phospholipase A2 in A23187-induced histamine release from purified rat mast cells

A23187-induced histamine release from purified rat mast cells is accompanied by degradation of mast cell phosphatidylcholine. When inhibitors of histamine release such as ethacrynic acid, eicosatetraynoic acid and phenylmethylsulfonylfluoride are added to the mast cell system, the phosphatidylcholine hydrolysis is inhibited along with the release of histamine. A simultaneous striking increase in prostaglandin D2 synthesis by the A23187-treated mast cells suggests that the degradation of phosphatidylcholine is associated with the activation of phospholipase A2. Arachidonic acid, one of the major products formed as a result of this activation, inhibits A23187 and antigen-induced histamine release when added 5 min prior to the histamine release inducers. Lysophosphatidylcholine, the other major product, demonstrates a biphasic effect, stimulating histamine release at low concentrations and inhibiting release at slightly higher concentrations. These findings suggest a histamine release regulating function for arachidonic acid and lysophosphatidylcholine.