Bridging of IgE receptors activates phospholipid methylation and adenylate cyclase in mast cell plasma membranes.

Abstract

Bridging of IgE receptors on normal rat mast cells by divalent anti-receptor antibodies induced phospholipid methylation and an increase in intracellular cAMP within 15 s after the receptor bridging. These biochemical events were followed by Ca2+ influx and histamine release. When IgE receptors on isolated plasma membranes were bridged by the antibody, both the increase in the incorporation of [3H]methyl into lipid fraction and the synthesis of cAMP were demonstrated. The synthesis of cAMP in this system was enhanced in the presence of GTP. Bridged IgE receptors are apparently linked to both methyltransferases and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the plasma membrane. An increase in cAMP prior to receptor bridging suppressed phospholipid methylation in the plasma membrane, Ca2+ uptake and subsequent histamine release. Inhibition of phospholipid methylation by (S)-isobutyryl-3-deazaadenosine resulted in the suppression of cAMP synthesis in the plasma membrane. The activation of phospholipid methylation and the activation of adenylate cyclase are apparently mutually regulated.