Inositol trisphosphate-independent agonist-stimulated calcium influx in rat pancreatic acinar cells

CCK-JMV-180 is a cholecystokinin analog that stimulates digestive enzyme secretion from pancreatic acinar cells but does not cause either generation of inositol 1,4,5-trisphosphate or depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca²⁺ storage pool. We report that CCK-JMV-180 can accelerate Ca²⁺ influx into fura-2-loaded dispersed rat pancreatic acini and single acinar cells. Furthermore, CCK-JMV-180 accelerates Ca²⁺ influx into cells microinjected with the inositol 1,4,5-trisphosphate receptor antagonist heparin and into acini loaded with the Ca²⁺-chelating agent BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). These results indicate that agonist-stimulated Ca²⁺ influx can occur (a) without depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca²⁺ storage pool, (b) without a rise in cytoplasmic free Ca²⁺ concentrations, and (c) after blockade of inositol 1,4,5-trisphosphate receptors. They suggest that depletion of an inositol 1,4,5-trisphosphate-independent intracellular Ca²⁺ storage pool and/or generation of a non-inositol 1,4,5-trisphosphate second messenger by CCK-JMV-180 may be a sufficient signal for acceleration of Ca²⁺influx into rat pancreatic acinar cells.