Calcium oscillations in pancreatic acinar cells, evoked by the cholecystokinin analogue JMV-180, depend on functional inositol 1,4,5-trisphosphate receptors.
It has been reported that the synthetic heptapeptide cholecystokinin (CCK) analogue JMV-180 evokes cytosolic Ca2+ signals in pancreatic acinar cells via mechanisms that do not include either the generation or action of inositol 1,4,5-trisphosphate (InsP3) (Saluja, A. K., Dawra, R. K., Lerch, M. M., and Steer, M. L. (1992) J. Biol. Chem. 267, 11202-11207; Yule, D. I., and Williams, J. A. (1992) J. Biol. Chem. 267, 13830-13835). We have now investigated the CCK- and JMV-180-evoked cytosolic Ca2+ oscillations by measurement of the Ca(2+)-sensitive ion currents in internally perfused mouse pancreatic acinar cells. We find that the InsP3 receptor antagonist heparin (500 micrograms/ml) blocks Ca2+ oscillations induced by both CCK (5-20 pM) and JMV 180 (10-40 nM), whereas de-N-sulfated heparin (500 micrograms/ml), which does not affect InsP3 binding to its receptor, fails to inhibit the responses to the two agonists. We conclude that the cytosolic Ca2+ oscillations evoked by both CCK and JMV-180 are dependent on functional InsP3 receptors.
Thorn
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Physiological Laboratory, University of Liverpool, United Kingdom.
Petersen
O H
OH
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000502:physiology*; D010507:Periodicity; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C058451:JMV 180; D006493:Heparin; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium