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Regulation of Intracellular Ca2+ in Pancreatic Acinar Cells by Membrane Pumps and Channels

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Molecular Basis of Membrane-Associated Diseases

Summary

Measurement and manipulation of cytoplasmic free Ca2+ in intact pancreatic acinar cells have suggested its primary role in regulating secretion in response to acetylcholine and cholecystokinin. Evidence suggests that Ca2+ is initially released from an intracellular store but increased Ca2+ entry is required for maintained stimulation. The mechanism of increased Ca2+ entry is unknown: no evidence for voltage- or receptor-operated channels has been found. Stimulation of Ins( 1, 4, 5)P3 and Ins(1, 3, 4, 5)P3 formation within 5 s of receptor occupancy supports recent data suggesting their involvement in activating Ca2+ entry. Intracellular Ca2+ release is accompanied by net loss of cellular Ca2+ released into the ductal secretions and actively extruded across the basolateral membrane. A Ca2+, Mg-ATPase and Na+/Ca2+ exchange has been demonstrated in purified plasma membranes but their properties do not allow a definition of which processes are most important physiologically.

Subcellular fractionation studies have suggested that the site of the intracellular Ca2+ store is a component of the rough endoplasmic reticulum, which, in the resting cell, is maintained by a Ca2+, Mg-ATPase and released following stimulation, by the action of Ins(1,4,5)P3. The mechanisms for Ca2+ release might include a Ca2+-activated component. Heterogeneity of Ca2+ stores and their mechanism of release from subcompartments of the endoplasmic reticulum may provide a link between Ca2+ release at a site closely apposed to the basolateral membrane and its release at sites nearer the apical end of the cell, causing activation of secretion.

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Dormer, R.L. (1989). Regulation of Intracellular Ca2+ in Pancreatic Acinar Cells by Membrane Pumps and Channels. In: Azzi, A., Drahota, Z., Papa, S. (eds) Molecular Basis of Membrane-Associated Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74415-0_8

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