title: Differential effects of maitotoxin on ATP secretion and on phosphoinositide breakdown in rat pheochromocytoma cells.
abstract: Maitotoxin (MTX) induced exocytotic secretion of ATP from PC12 rat pheochromocytoma cells. The threshold for stimulation of secretion was at concentrations of about 2 ng/ml of MTX. Maximal release occurred at 40 ng/ml. MTX-induced ATP release required the presence of calcium in the extracellular medium and could be inhibited by nifedipine, a specific blocker of voltage-dependent calcium channels. In addition to the effects on ATP secretion from PC12 cells, MTX stimulated the breakdown of phosphoinositides, as measured by the accumulation of [3H]inositol phosphates. Maximal stimulation of phosphoinositide breakdown was reached at only 0.5-1.0 ng/ml MTX. MTX at concentrations required to evoke ATP release (greater than 2 ng/ml) had lesser or no effect on phosphoinositide breakdown. Although stimulation of phosphoinositide breakdown by MTX was dependent on extracellular calcium, it was insensitive to the calcium channel blockers nifedipine, D-600 and cobalt ions. The different concentration range required to elicit these responses and the varying sensitivity to calcium channel blockers indicate that MTX-evoked secretion and MTX-stimulated phosphoinositide breakdown are independent phenomena in PC12 cells.
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, Bethesda, MD 20892.
authors.forename: F
authors.initials: F
authors.lastname: Gusovsky
authors.forename: J W
authors.initials: JW
authors.lastname: Daly
authors.forename: T
authors.initials: T
authors.lastname: Yasumoto
authors.forename: E
authors.initials: E
authors.lastname: Rojas
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D008387:Marine Toxins / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D035964:Oxocins; D010673:Pheochromocytoma / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D000095702:Polyether Toxins
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium; D007295:Inositol Phosphates; D008387:Marine Toxins; D009543:Nifedipine; D035964:Oxocins; D010716:Phosphatidylinositols; C020394:maitotoxin; D000095702:Polyether Toxins