INTRACELLULAR CALCIUM RESPONSES IN CF T43 CELLS - CALCIUM POOLS AND INFLUX PATHWAYS/

We studied the intracellular free Ca2+ concentration ([Ca2+](i)) respo nse to histamine in a cystic fibrosis airway epithelial cell line (CF/ T43). Histamine (100 mu M; duration similar to 10 min) biphasically in creased [Ca2+](i), with a rapid initial peak (30-45 s) followed by a s maller second peak that lasted for several minutes before returning to baseline. Neither peak specifically depended on Ca2+ influx. Exposure to bradykinin (10 mu M) elicited a single peak that lasted 3-3.5 min before returning to baseline. Bradykinin increased intracellular inosi tol 1,4,5-trisphosphate (IP3), which peaked and returned to baseline w ithin 150 s. Histamine also increased IP3 monophasically, but the peak was brief(<20 s). Both phases of the Ca2+ response to histamine exhib ited similar responsiveness to histamine concentration and sensitivity to antagonists. Cimetidine or thioperamide (1 mM) had no effect on th e second peak. Pyrilamine blocked the second peak at concentrations si milar to those required to block the initial peak. Activation of the s econd peak was observed at a threshold concentration of 1 mu M compara ble with the threshold of the initial peak. Neither adenosine 3',5'-cy clic monophosphate, guanosine 3',5'-cyclic monophosphate, nor cyclic A DP (cADP) ribose altered the second phase of the histamine response.