CCK-JMV-180, an analog of cholecystokinin, releases intracellular calcium from an inositol trisphosphate-independent pool in rat pancreatic acini

In pancreatic acinar cells cholecystokinin and its analogs, caerulein and CCK-JMV-180, stimulate an increase in intracellular free [Ca²⁺] by releasing Ca²⁺ from non-mitochondrial intracellular pools. It is generally believed that the caerulein-induced release of Ca²⁺ is mediated by phospholipase C-catalyzed production of 1,4,5-inositol trisphosphate (IP₃). In this study we have investigated the source and mechanism of Ca²⁺ release induced by CCK-JMV-180 using streptolysin O-permeabilized pancreatic acinar cells. Caerulein-stimulated release of Ca²⁺ was completely blocked by either neomycin, an inhibitor of phospholipase C, or by heparin, an IP₃ receptor antagonist. These observations are compatible with the conclusion that caerulein releases Ca²⁺ from an IP₃-sensitive pool. In contrast to caerulein, however, CCK-JMV-180-stimulated release of Ca²⁺ was not blocked by either neomycin or by heparin, indicating that CCK-JMV-180 releases Ca²⁺ by mechanisms which do not involve the generation or action of IP₃. CCK-JMV- 180 stimulated the release of Ca²⁺ even after the IP₃-sensitive pool had been completely emptied by prior exposure to a supramaximally stimulating concentration of IP₃ (40 μM). Prestimulation of permeabilized acini with 20 mM caffeine did not abolish the CCK-JMV-180-induced Ca²⁺ release. These results indicate that CCK-JMV-180 stimulates release of Ca²⁺ from a hitherto uncharacterized intracellular storage pool which is insensitive to either IP₃ or caffeine.