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 Ca(2+)-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.