Inositol trisphosphate-independent agonist-stimulated calcium influx in rat pancreatic acinar cells.
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.
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts.
R K
RK
Dawra
A K
AK
Saluja
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Rünzi
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ML
Steer
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002108:Ceruletide / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016257:Fura-2; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
C058451:JMV 180; D008345:Manganese; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002108:Ceruletide; D006493:Heparin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D012844:Sincalide; D002118:Calcium; D016257:Fura-2