Novel interactions between second messengers in rat basophilic leukaemia (RBL-1) cells

As a continuation of our efforts to understand leukotriene biosynthesis mechanisms, we have studied the effect on RBL-1 cells of a series of phospholipase C (PLC) and phospholipase A2 (PLA2) activators including calcium ionophore (A23187), leukotriene D4 (LTD4), PAF, fMLP and bradykinin. LTD4 and A23187 (the latter only at 20 microM concentration and only after a 45 min incubation time) were shown to induce phosphoinositide (PI) breakdown, whilst A23187 induced leukotriene biosynthesis. For the first time it was shown that cAMP analogues markedly inhibit LTD4-induced IP formation. Moreover, the 5-lipoxygenase inhibitor AA861 abolished the ionophore-induced PI breakdown, thus suggesting that this effect is a novel example of PLC activation following PLA2 activation and 5-lipoxygenase-derived metabolite production.