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.
Galadari
S H
SH
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K.
Morris
H R
HR
Di Marzo
V
V
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D007295:Inositol Phosphates / Q000096:biosynthesis; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology*; D015289:Leukotrienes / Q000096:biosynthesis*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D013189:SRS-A / Q000494:pharmacology; D015290:Second Messenger Systems; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D015289:Leukotrienes; D010972:Platelet Activating Factor; D013189:SRS-A; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D001920:Bradykinin