Cholecystokinin-induced phosphatidylinositol hydrolysis in rat pancreatic acinar cells: modulation by extracellular calcium and manganese.
The role of extracellular calcium in modulating the actions of cholecystokinin octapeptide (CCK8) on phosphatidylinositol 4,5-bisphosphate hydrolysis was studied in freshly isolated rat pancreatic acini and cultured AR42J cells. In both cell types, CCK8 rapidly induced the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and 1,3,4, 5-tetrakisphosphate [Ins(1,3,4,5)P4]. The actions of CCK8 were inhibited by lanthanum and manganese, agents that block transmembrane calcium fluxes, and by chelation of extracellular calcium with EGTA. In pancreatic acini, lanthanum and manganese also partially inhibited the effects of carbachol and bombesin on Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels. In acini, the CCK8-mediated increases in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels were progressively greater as the extracellular calcium concentration was raised from the micromolar range to 1.28 mM and progressively smaller as the manganese concentration was raised from 10 microM to 1 mM. Furthermore, the CCK8-mediated rise in Ins(1,4,5)P3 levels was partially attenuated by the calcium channel blockers verapamil, diltiazem, and nifedipine. These findings indicate that extracellular calcium enhances the ability of CCK8 and other calcium-mobilizing agonists to generate biologically active inositol phosphates in pancreatic acinar cells.
Korc
M
M
Department of Medicine, University of California, Irvine 92717.
Chandrasekar
B
B
Siwik
S A
SA
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D004110:Diltiazem / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; C081655:inositol-1,3,4,5-tetrakisphosphate; D008345:Manganese; D004533:Egtazic Acid; D007811:Lanthanum; D015544:Inositol 1,4,5-Trisphosphate; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D012844:Sincalide; D002118:Calcium