CA2-ATPASE INHIBITOR, CYCLOPIAZONIC ACID, RELEASES CA2+ FROM INTRACELLULAR STORES IN RBL-2H3 MAST-CELLS AND ACTIVATES A CA2+ INFLUX PATHWAYTHAT IS PERMEABLE TO SODIUM AND MANGANESE()

Cyclopiazonic acid has been reported to inhibit the Ca2+-ATPase of int racellular calcium stores in some nonexcitable cell types, such as mye loid cells and lymphocytes. The present study examines the effects of cyclopiazonic acid on rat basophilic leukemia (RBL) cells, a mucosal m ast cell line. Addition of cyclopiazonic acid to fura-2-loaded RBL cel ls evoked a biphasic increase in free ionized intracellular calcium. R elease of stored calcium accounted for the first phase of this respons e. The second phase was determined to be calcium entering through an i nflux pathway activated by cyclopiazonic acid. The influx pathway was selective for calcium, but was somewhat permeable to manganese. Howeve r, in a Ca2+ free solution containing EGTA, sodium ions permeated free ly. This influx pathway appears to be identical to that which is activ ated by antigen, the physiological stimulus to the cells. Cyclopiazoni c acid also induced secretion when combined with the phorbol ester 12- O-tetradecanoyl phorbol 13-acetate, which activates protein kinase C. (C) 1995 Wiley-Liss, Inc.