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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Gardner JD, Jensen RT (1986) Receptors and cell activation with pancreatic enzyme secretion. Annu Rev Physiol 48:103–117
Williams JA, Sankaran H, Roach E, Goldfine ID (1982) Quantitative electron microscope autoradiographs of 125cholecystokinin in pancreatic acini. Am J Physiol 243:G291–G296
Petersen OH (1986) Calcium-activated potassium channels and fluid secretion by exocrine glands. Am J Physiol 151:G1–G13
Petersen OH, Gallacher DV (1988) Electrophysiology of pancreatic and salivary acinar cells. Annu Rev Physiol 50:65–80
Bundgaard M, Moller M, Poulsen JH (1981) Localization of sodium pump sites in cat pancreas. J Physiol London 313:405–414
Maruyama Y, Petersen OH, Flanagan P, Pearson GT (1983) Quantification of Ca2 +-activated K+ channels under hormonal control in pig pancreas acinar cells. Nature (London) 305:228–232
Petersen OH, Findlay I, Iwatsuki I, Singh J, Gallacher DV, Fuller CM, Pearson GT, Dunne MJ, Morris AP (1985) Human pancreatic acinar cells: studies of stimulus-secretion coupling. Gas-troenterology 89:109–117
Maruyama Y, Petersen OH (1984) Single calcium-dependent cation channels in mouse pancreatic acinar cells. J Membrane Biol 81:83–87
Palade GE (1975) Intracellular aspects of the process of protein synthesis. Science 189:347–358
Dormer RL, Hallett MB, Campbeil AK (1985) Measurement of intracellular free Ca2+: importance during activation and injury of small cells In: Parratt JR (ed) Control and manipulation of calcium movement. Raven, New York, pp 1–27
Dormer RL, Brown GR, Doughney C, McPherson MA (1987) Intracellular Ca2+ in pancreatic acinar cells: regulation and role in stimulation of enzyme secretion. Biosci Rep 7:333–344
Tsien RY, Pozzan T, Rink TJ (1982) Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol 94:325–334
Ochs DL, Korenbrot JI, Williams JA (1985) Relation between free cytosolic calcium and amylase release by pancreatic acini. Am J Physiol 249:G389–G398
Bruzzone R, Pozzan T, Wollheim CB (1986) Caerulein and cabamylcholine stimulate pancreatic amylase release at resting cytosolic free Ca2 +. Biochem J 235:139–143
Pandol SJ, Schoeffield MS, Sachs G, Muallem S (1985) Role of cytosolic calcium in secre-tagogue-stimulated amylase release from dispersed acini from guinea-pig pancreas. J Biol Chem 260:10081–10086
Powers RE, Johnson PC, Houlihan MJ, Saluja AK, Steer ML (1985) Intracellular Ca2+ levels and amylase secretion in Quin-2-loaded mouse pancreatic acini. Am J Physiol 248:C535–C541
Merritt JE, Rubin RP (1985) Pancreatic amylase secretion and cytoplasmic free calcium. Effects of ionomycin, phorboldibutyrate and diacylglycerols alone and in combination. Biochem J 230:151–159
Eimerl S, Savion N, Heichal O, Selinger Z (1974) Induction of enzyme secretion in rat pancreatic slices using the ionophore A23187 and Ca2+. J Biol Chem 249:3991–3993
Williams JA, Lee M (1974) Pancreatic acinar cells: use of a Ca2+ ionophore to separate enzyme release from earlier steps in stimulus-secretion coupling. Biochem Biophys Res Commun 60:542–548
Donner RL (1983) Direct demonstration of increases in cytosolic free Ca2 + during stimulation of pancreatic enzyme secretion. Biosci Rep 3:233–240
Iwatsuki I, Petersen OH (1977) Acetylcholine-like effects of intracellular Ca2+ application in pancreatic acinar cells. Nature (London) 268:147–149
Dormer RL (1984) Introduction of calcium chelators into isolated rat pancreatic acini inhibits amylase release in response to carbamylcholine Biochem. Biophys Res Commun 119:876–883
Laugier R, Petersen OH (1980) Effects of intracellular EGTA injection on stimulant-evoked membrane potential and resistance changes in pancreatic acinar cells. Pflüger’s Arch 386:147–152
Bruzzone R, Regazzi R, Wollheim CB (1988) Caerulein causes translocation of protein kinase C in rat pancreatic acini without increasing cytosolic free Ca2+ Am J Physiol 255:G1–G7
Chandler DE, Williams JA (1977) Intracellular uptake and a-amylase and LDH releasing actions of divalent cation ionophore A23187 in dissociated pancreatic acinar cells. J Membrane Biol 32:201–230
Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature (London) 308:693–698
Gunther GR (1981) Effects of 12-0-tetradecanoyl-phorbol-13-acetate on Ca2+ efflux and protein discharge in pancreatic acini. J Biol Chem 256:12040–12045
De Pont JJHHM, Fleurens-Jakobs AMM (1984) Synergistic effect of A23187 and a phorbol ester on amylase secretion from rabbit pancreatic acini. FEBS Lett 170:64–68
Knight DE, Koh E (1984) Ca2 + and cyclic nucleotide dependence of amylase release from isolated rat pancreatic acinar cells rendered permeable by intense electric fields. Cell Calcium 5:401–418
Petersen OH, Ueda N (1976) Pancreatic acinar cells: the role of calcium in stimulus-secretion coupling. J Physiol London 254:583–606
Gardner JD, Costenbader CL, Uhlemann ER (1979) Effect of extracellular Ca2+ on amylase release from dispersed pancreatic acini. Am J Physiol 236:E754–E762
Scheele G, Haymovits A (1979) Cholinergic and peptide-stimulated discharge of secretory proteins in guinea-pig pancreatic lobules. J Biol Chem 254:10346–10353
Williams JA (1980) Regulation of pancreatic acinar cell function by intracellular calcium. Am J Physiol 238:G269–G279
Case RM, Clausen T (1973) Relationship between calcium exchange and enzyme secretion in isolated rat pancreas. J Physiol London 235:75–102
Williams JA, Chandler DE (1975) Ca2+ and pancreatic amylase release. Am J Physiol 228:1729–1732
Kondo S, Schulz I (1976) Calcium fluxes in isolated cells of rat pancreas. Effect of secretagogues and different calcium concentrations. J Membrane Biol 29:185–203
Dormer RL, Poulsen JH, Licko V, Williams JA (1981) Calcium fluxes in isolated pancreatic acini: effect of secretagogues. Am J Physiol 240:G38–G49
Renckens BAM, Schrijen JJ, Swarts HGP, De Pont JJHHM, Bonting SL (1978) Role of calcium in exocrine pancreatic secretion. IV. Calcium movements in isolated acinar cells of rabbit pancreas. Biochim Biophys Acta 544:338–350
Stolze H, Schulz I (1980) Effect of atropine, ouabain, antimycin A and A32187 on “trigger Ca2+ pool” in exocrine pancreas. Am J Physiol 238:G338–G348
Kondo S, Schulz I (1976) Calcium ion uptake in isolated pancreatic cells induced by secretagogues. Biochim Biophys Acta 419:76–92
Borle AB (1969) Kinetic analyses of Ca2+ movement in Hela cell cultures: I: Ca2+ influx. J Gen Physiol 53:43–56
Lamb JF, Lindsay R (1971) Effect of sodium, metabolic inhibitors and ATP on calcium movements in L cells. J Physiol London 218:691–708
Petersen OH, Maruyama Y (1983) What is the mechanism of the calcium influx to pancreatic acinar cells evoked by secretagogues. Pflüger’s Arch 396:82–84
Godfraind T, Miller R, Wibo M (1986) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38:321–416
Petersen OH (1980) The electrophysiology of gland cells. Academic Press, New York London
Suzuki K, Petersen CCH, Petersen OH (1985) Hormonal activation of single K+ channels via internal messenger in isolated pancreatic acinar cells. FEBS Lett 192:307–312
Irvine RF, Moor RM (1986) Microinjection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J 240:917–920
Morris AP, Gallacher DV, Irvine RF, Petersen OH (1987) Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels. Nature (London) 330:653–655
Doughney C, Brown GR, McPherson MA, Donner RL (1987) Rapid formation of inositol-1, 4, 5-trisphosphate in rat pancreatic acini stimulated by carbamylcholine. Bibchim Biophys Acta 928:341–348
Trimble ER, Bruzzone R, Mechan CJ, Biden TJ (1987) Rapid increases in inositol 1,4,5-tris-phosphate, inositol 1, 3, 4, 5-tetrakisphosphate and cytosolic free Ca2+ in agonist-stimulated pancreatic acini of the rat. Effect of carbachol, caerulein and secretin. Biochem J 242:289–292
Schatzmann HJ (1982) The plasma membrane calcium pump of erythrocytes and other animal cells. In: Carafoli E (ed) Membrane transport of calcium. Academic Press, New York London, pp 41–108
Lin S-H (1985) Novel ATP-dependent calcium transport component from rat liver plasma membranes. The transporter and the previously reported (Ca2+ +Mg2+)-ATPase are different proteins. J Biol Chem 260:7850–7856
Minami J, Penniston JT (1987) Ca2+ uptake by corpus luteum plasma membranes. Evidence for the presence of both a Ca2 +-pumping ATPase and Ca2+-dependent nucleoside triphosphatase. Biochem J 242:889–894
Hamlyn JM, Senior AE (1983) Evidence that Mg2+-or Ca2+-activated adenosine triphosphatase in rat pancreas is a plasma membrane ecto-enzyme. Biochem J 214:59–68
Ansah TA, Molla A, Katz S (1984) Ca2+-ATPase activity in pancreatic acinar plasma membranes. Regulation by calmodulin and acidic phospholipids. J Biol Chem 259:13442–13450
Dormer RL, Al-Mutairy AR (1987) Pancreatic acinar cell plasma-membrane enzymes involved in stimulus-secretion coupling. In: Reid E, Cook BMW, Luzio JP (eds) Cells, membranes and disease, including renal. Plenum, New York, pp 273–283
Bayerdorffer E, Eckhardt L, Haase W, Schulz I (1985) Electrogenic calcium transport in plasma membranes of rat pancreatic acinar cells. J Membrane Biol 84:45–60
Blaustein MP, Nelson MT (1982) Sodium-calcium exchange: its role in the regulation of cell calcium. In: Carafoli E (ed) Membrane transport of calcium. Academic Press, New York London, pp 217–236
Bayerdorffer E, Haase W, Schulz I (1985) Na+ /Ca2 + countertransport in plasma membrane of rat pancreatic acinar cells. J Membrane Biol 87:107–119
Williams JA (1980) Multiple effects of Na+ removal on pancreatic secretion in vitro. Cell Tissue Res 210:295–303
Muallem S, Beeker T, Pandol SJ (1988) Role of Na+ /Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini. J Membrane Biol 102:153–162
Goebell H, Steffen Ch, Bode Ch (1972) Stimulatory effect of pancreozymin-cholecystokinin on calcium secretion in pancreatic juice of dogs. Gut 13:477–482
Ceccarelli B, Clemente F, Meldolesi J (1975) Secretion of calcium in pancreatic juice. J Physiol London 245:617–638
Argent BE, Case RM, Scratcherd T (1973) Amylase secretion by perfused cat pancreas in relation to secretion of calcium and other electrolytes and as influenced by external ionic environment. J Physiol London 230:575–593
Schreurs VVAM, Swarts HGP, De Pont JJHHM, Bonting SL (1975) Role of Ca2+ in exocrine pancreatic secretion. I. Calcium movements in the rabbit pancreas. Biochim Biophys Acta 404:257–267
Layer P, Holtz J, Goebell H (1983) Calcium secretion from the feline pancreas. Digestion 26:89–98
Dormer RL, Mann GE, Norman PSR (1987) Comparison of calcium efflux from isolated rat pancreatic acini and perfused pancreas: effects of carbachol. J Physiol London 390:100P
Clemente F, Meldolesi J (1975) Calcium and pancreatic secretion. Dynamics of subcellular calcium pools in resting and stimulated acinar cells. Br J Pharmacol 55:369–379
Dormer RL, Williams JA (1981) Secretagogue-induced changes in subcellular Ca2+ distribution in isolated pancreatic acini. Am J Physiol 240:G130–G140
Brown GR, Richardson AE, Dormer RL (1987) The role of a (Ca2+ +Mg2+)-ATPase of the rough endoplasmic reticulum in regulating intracellular Ca2+ during cholinergic stimulation of rat pancreatic acini. Biochim Biophys Acta 902:87–92
Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature (London) 312:315–321
Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1, 4, 5-trisphosphate. Nature (London) 306:67–69
Streb H, Bayerdorffer E, Haase W, Irvine RF, Schulz I (1984) Effect of inositol-1, 4, 5-trisphosphate on isolated subcellular fractions of rat pancreas. J Membrane Biol 81:241–253
Schulz I, Wakasugi H, Stolze H, Kribben A, Haase W (1981) Analysis of Ca2+ fluxes and then-relation to enzyme secretion in dispersed pancreatic acinar cells. Fed Proc 40:2503–2510
Schulz I, Kimura T, Wakasugi H, Haase W, Kribben A (1981) Analysis of Ca2+ fluxes and Ca2+ pools in pancreatic acini. Philos Trans Soc Lond Ser B 296:105–113
Henne V, Piiper A, Soling H-D (1987) Inositol-1, 4, 5-trisphosphate and 5′-GTP induce calcium release from different intracellular pools. FEBS Lett 218:153–158
Volpe P, Krause K-H, Hashimoto S, Zorzato F, Pozzan T, Meldolesi J, Lew DP (1988) “Calciosome”, a cytoplasmic organelle: the inositol-1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells? Proc Natl Acad Sci USA 85:1091–1095
MacLennan DH, Campbell KP, Reithmeier RAF (1983) Calsequestrin. In: Cheung WY (ed) Calcium and cell function, vol 4. Academic Press, New York London, pp 151–173
Putney JW (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12
Meissner G (1984) Adenine nucleotide stimulation of Ca2 +-induced Ca2 + release in sacroplasmic reticulum. J Biol Chem 259:2365–2374
Fabiato A (1983) Ca2+-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:C1–C14
McPherson MA, Goodchild MC (1988) The biochemical defect in cystic fibrosis. Clin Sci 74:337–345
McPherson MA, Dormer RL (1987) The molecular and biochemical basis of cystic fibrosis. Biosci Rep 7:167–185
McPherson MA, Dormer RL (1988) Cystic fibrosis: a defect in stimulus response coupling. TIBS 13:10–13
McPherson MA, Shori DK, Dormer RL (1988) Defective regulation of apical membrane chloride transport and exocytosis in cystic fibrosis. Biosci Rep 8:27–33
Al-Mutairy AR, Dormer RL (1985) Isolation of plasma membranes from pancreatic acinar cells: demonstration of a Ca2+-activated Mg2+-ATPase activity. Biochem Soc Trans 13:900–901
Richardson AE, Dormer RL (1984) Calcium-ion-transporting activity in two microsomal sub-fractions from rat pancreatic acini. Modulation by carbamylcholine. Biochem J 219:679–685
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/978-3-642-74415-0_8
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-74417-4
Online ISBN: 978-3-642-74415-0
eBook Packages: Springer Book Archive