Compound 48/80の活性オリゴマーによる肥満細胞からのヒスタミン分泌機構とリン脂質代謝について

抄録

We synthesized compound 48/80, and fractionated by TLC into 14 components with various histamine-releasing activities and different Ca²⁺-requirements for their actions. The effect of active component was investigated on phospholipid metabolism during the postreceptorligand-binding in relation to the Ca²⁺-dependent histamine release from mast cells. The most active component (MW=2280, a tridecamer of N-methyl-p-methoxyphenylethylamine monomer) induced the Ca²⁺-dependent histamine release from mast cells, via its binding to a specific sites on the membranes. The binding reaction, a Ca²⁺ -independent process, induced the Ca²⁺-independent changes of polyphosphoinositol cv le including the hydrolysis of PIP₂ and IP₃ formation. On the other hand, it stimulated Ca²⁺-dependent releases of arachidonic acid, prostaglandins and HETEs. Kinetic analysis suggests that the binding of ligand to receptor induced a rapid accumlation of arachidonic acid into PA, PI and PC, with concomitant decrease of the arachiodonic acid from PE, following a Ca²⁺-dependent increase of phospholipase A₂, prior to the detectable histamine release.