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

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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.
日本膜学会の論文