Role of calcium in cholecystokinin-stimulated phosphoinositide breakdown in exocrine pancreas.
In dispersed acini from guinea pig pancreas cholecystokinin octapeptide (CCK-OP) stimulated breakdown of the phosphoinositides phosphatidylinositol (PI) and its phosphorylated derivative, phosphatidylinositol 4,5-bisphosphate (PI-P2), as measured by a decrease in the mass of PI and decreases in the content of [3H]PI and [32P]PI-P2 in acini prelabeled with myo-[2-3H]inositol or H3(32)PO4. The breakdown occurred in the absence of extracellular Ca2+ and when the CCK-OP-induced rise in free intracellular Ca2+ ([Ca2+]i) was ablated by loading the acini with the Ca2+-selective indicator and chelator quin-2 in the absence of extracellular Ca2+. In contrast to CCK-OP, the calcium ionophore A23187 caused breakdown of PI and PI-P2 in the presence but not in the absence of extracellular Ca2+, although like CCK-OP A23187 stimulated 45Ca outflux, a measure of cellular Ca2+ mobilization, and amylase release during the first 5-10 min of incubation independent of extracellular Ca2+. In the absence of extracellular Ca2+ A23187 did not inhibit the ability of CCK-OP to cause PI breakdown. These results indicate that CCK-OP stimulates breakdown of PI and PI-P2 and that this breakdown is independent of extracellular Ca2+, mobilization of intracellular Ca2+, and the CCK-OP-induced rise in [Ca2+]i. These findings suggest that one of the initial events resulting from CCK-OP interaction with its receptor is phosphoinositide breakdown.
Pandol
S J
SJ
Thomas
M W
MW
Schoeffield
M S
MS
Sachs
G
G
Muallem
S
S
D000634:Aminoquinolines / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology
D000634:Aminoquinolines; D010716:Phosphatidylinositols; D000001:Calcimycin; D004533:Egtazic Acid; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide; C035739:Quin2; D002118:Calcium