Maitotoxin, a potent, general activator of phosphoinositide breakdown.
Maitotoxin (MTX), a potent marine toxin, elicits a calcium-dependent activation of cells that can be inhibited by calcium channel blockers like nifedipine. MTX also stimulates phosphoinositide breakdown in smooth muscle cells, NCB-20 cells and PC12 cells through a nifedipine-insensitive mechanism. We now report that MTX stimulates phosphoinositide breakdown in a wide variety of cells, and appears to represent the first general activator of this second messenger-generating system. MTX-induced stimulation of phosphoinositide breakdown is dependent in every cell line on the presence of extracellular calcium. In differentiated HL60 cells, in which a chemotactic peptide (fMLP) activates phosphoinositide breakdown via a pertussis toxin-sensitive mechanism, MTX-induced stimulation is not affected by pertussis toxin treatment. A phorbol ester has no effect on the response to MTX. Thus, MTX stimulates phosphoinositide breakdown through a calcium-dependent mechanism that at least in three cell lines (PC12, NCB20 and HL60) is not mediated by a pathway that involves a pertussis toxin-sensitive guanine nucleotide-binding protein.
Gusovsky
F
F
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Yasumoto
T
T
Daly
J W
JW
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008387:Marine Toxins / Q000494:pharmacology*; D035964:Oxocins; D010716:Phosphatidylinositols / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D010738:Type C Phospholipases / Q000502:physiology; D000095702:Polyether Toxins
D002118:Calcium; D008387:Marine Toxins; D035964:Oxocins; D010716:Phosphatidylinositols; D010738:Type C Phospholipases; C020394:maitotoxin; D000095702:Polyether Toxins