Effect of the tridecamer of compound 48/80, a Ca2+-dependent histamine releaser, on phospholipid metabolism during the early stage of histamine release from rat mast cells

Abstract

When the tridecamer component of compound 48/80 (Fraction D, Fr. D), a Ca2+-dependent histamine releaser, was incubated with rat mast cells that had been prelabeled with [32P]phosphate, [3H]inositol or [3H]glycerol, it induced a rapid decrease in [32P]phosphatidylinositol-4,5-bisphosphate (PIP2) followed by increases of [3H]inositol-1,4,5-triphosphate (Ins P3) and [3H]diacylglycerol during the 10 sec prior to detectable histamine release. Fr.D-induced changes of the metabolism of these compounds occurred even in the absence of Ca2+, but to a lesser extent than in the presence of Ca2+. In contrast, the accumulation of [3H]arachidonic acid into phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidic acid (PA) in [3H]arachidonic acid-prelabeled mast cells was Ca2+-dependently stimulated by Fr.D with a concomitant decrease in [3H]phophatidylethanolamine (PE). These Ca2+-dependent changes in PC and PE were not observed in mast cells preloaded with [32P]phosphate, while [32P]PI and [32P]PA increased Ca2+ independently. Fr.D also increased 45Ca2+ uptake by mast cells within 5 sec after the stimulation. These results indicate that Fr.D binding to mast cell Ca2+ independently induces rapid changes of PI cycle-related metabolism of plasma membrane components, while it also induces Ca2+-dependent accumulation of arachidonic acid into PC, PI and PA in association with the decrease of PE, which may be important during the latent period prior to the Ca2+-dependent release of histamine from Fr.D-stimulated mast cells.