The purpose of this proposal is to elucidate the mechanism through which the reaction of antigen with cell-bound IgE antibody leads to the release of chemical mediators from mast cells. Research plan is based on our recent findings which indicated that bridging of IgE-receptors by divalent anti-receptor antibody stimulated phospholipid methylation at the membrane, and that this process set a stage for opening Ca ion-channels and subsequent histamine release. We shall study 1) as to whether the phospholipid methylation is controlled by intracellular cyclic AMP level, and 2) whether methyltransferases are the first enzymes to be activated by receptor bridging. 3) Possible role of methyltransferases in the process of "desensitization" will be studied. Another question to be asked is how phospholipid methylation leads to opening of Ca-channels. 4) Considering possible role of phospholipase A2 in the process of mediator release, we shall investigate pharmacological effect of glucocorticoid in the biochemical process.