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 triphosphate (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 microM). 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.
Saluja
A K
AK
Harvard Medical School, Harvard Digestive Diseases Center, Boston, Massachusetts.
Dawra
R K
RK
Lerch
M M
MM
Steer
M L
ML
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
C058451:JMV 180; D002110:Caffeine; D014638:Vanadates; D015544:Inositol 1,4,5-Trisphosphate; D002108:Ceruletide; D006493:Heparin; D010738:Type C Phospholipases; D000681:Amylases; D009355:Neomycin; D012844:Sincalide; D002118:Calcium