Ca(2+)-ATPase inhibitor, cyclopiazonic acid, releases Ca2+ from intracellular stores in RBL-2H3 mast cells and activates a Ca2+ influx pathway that is permeable to sodium and manganese.
Cyclopiazonic acid has been reported to inhibit the Ca(2+)-ATPase of intracellular calcium stores in some nonexcitable cell types, such as myeloid cells and lymphocytes. The present study examines the effects of cyclopiazonic acid on rat basophilic leukemia (RBL) cells, a mucosal mast cell line. Addition of cyclopiazonic acid to fura-2-loaded RBL cells evoked a biphasic increase in free ionized intracellular calcium. Release of stored calcium accounted for the first phase of this response. The second phase was determined to be calcium entering through an influx pathway activated by cyclopiazonic acid. The influx pathway was selective for calcium, but was somewhat permeable to manganese. However, in a Ca(2+)-free solution containing EGTA, sodium ions permeated freely. This influx pathway appears to be identical to that which is activated by antigen, the physiological stimulus to the cells. Cyclopiazonic acid also induced secretion when combined with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate, which activates protein kinase C.
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Department of Pharmacology, Cornell University, Ithaca, New York 14853-6401, USA.
Fewtrell
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002463:Cell Membrane Permeability; D007211:Indoles / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D009994:Osmolar Concentration; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007211:Indoles; D008345:Manganese; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid