Maitotoxin-elicited calcium influx in cultured cells. Effect of calcium-channel blockers.
Maitotoxin elicited a marked influx of 45Ca2+ into NIH 3T3 fibroblast cells. The influx was blocked by imidazoles (econazole, miconazole, SKF 96365, clotrimazole, calmidazolium) with IC50 values from 0.56 to 3 microM. Phenylalkylamines (verapamil, methoxyverapamil) and nitrendipine were less potent, and diltiazem was very weak. Among other calcium blockers, the diphenylbutylpiperidines fluspirilene and penfluridol, the diphenylpropylpiperidine loperamide, and the local anesthetic proadifen were quite active with IC50 values of 2-4 microM. The pattern of inhibition of maitotoxin-elicited calcium influx did not correspond to the ability of the agents to block elevation of calcium that ensues through calcium-release activated calcium (CRAC) channels after activation of phosphoinositide breakdown by ATP in HL-60 cells. The imidazoles did block CRAC channels, but fluspirilene, penfluridol, loperamide and proadifen were ineffective. Loperamide actually appeared to enhance influx of calcium via the activated CRAC channels. The imidazoles, in particular calmidazolium, caused an apparent influx of calcium and caused a stimulation of phosphoinositide breakdown in HL-60 cells.
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000096:biosynthesis; D002132:Calcium Radioisotopes; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D035964:Oxocins; D010716:Phosphatidylinositols / Q000378:metabolism; D000095702:Polyether Toxins
D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007093:Imidazoles; D008387:Marine Toxins; D035964:Oxocins; D010716:Phosphatidylinositols; C020394:maitotoxin; D000095702:Polyether Toxins