Summary
The effects of the Ca2+ ionophore A 2317 on pancreatic amylase and lactate dehydrogenase (LDH) release, cellular electrolyte balance and ultra-structure were studied with the use of incubated pancreatic fragments. A 23187 (0.3 μM) in the presence of Ca2+, increased amylase release but at higher concentrations (1–10 μM) also increased LDH release and increased uptake of 14C-sucrose with concomitant loss of tissue K+ and gain in Na +. The ultrastructure of the majority of acini appeared normal and showed depletion of zymogen granules. Microtubules and microfilaments which have been implicated in the release process were normal or increased in number. In the absence of Ca+ the ionophore had no effect on secretion, cellular integrity or ultrastructure. It is concluded that A 23187 in the presence of Ca2+ increases amylase release by a mechanism comparable to the terminal steps in stimulussecretion coupling induced by physiological secretagogues. This provides further evidence that amylase release is mediated by a rise in cell Ca2+ although the mechanisms of the ionophore- and physiological secretagogue-induced rise in Ca+ are probably different. High concentrations of ionophore (> 1 μM) also induce Ca2+ dependent damage in a fraction of the cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Babcock, D.F., First, N.L., Lardy, H.A.: Action of ionophore A 23187 at the cellular level. Separation of effects at the plasma and mitochondrial membranes. J. biol. Chem. 251, 3881–3886 (1976)
Bauduin, H., Stock, C., Vincent, D., Grenier, J.F.: Microfilamentous system and secretion of enzyme in the exocrine pancreas. Effect of cytochalasin B. J. Cell Biol. 66, 165–181 (1975)
Chandler, D.E., Williams, J.A.: Intracellular uptake and α-amylase and lactate dehydrogenase releasing actions of the divalent cation ionophore A 23187 in dissociated pancreatic acinar cells. J. Membrane Biol. 32, 201–230 (1977)
Christophe, J.P., Frandsen, E.K., Conlon, T.P., Krishna, G., Gardner, J.D.: Action of cholecystokinin, cholinergic agents, and A 23187 on accumulation of guanosine 3′ ∶ 5′-monophosphate in dispersed guinea pig pancreatic acinar cells. J. biol. Chem. 251, 4640–4645 (1976)
Gaskin, F., Cantor, C.R., Shelanski, M.L.: Biochemical studies on the in vitro assembly and disassembly of microtubules. Ann. N.Y. Acad. Sci. 253, 133 (1975)
Kaiser, N., Edelman, I.S.: Calcium dependence of glucocorticoid-induced lymphocytolysis. Proc. nat. Acad. Sci. (Wash.) 74, 638–642 (1977)
Reed, P.W.: Effects of the divalent cation ionophore A 23187 on potassium permeability of rat erythrocytes. J. biol. Chem. 251, 3489–3494 (1976)
Reed, P.W., Lardy, H.A.: A23187: A divalent cation ionophore. J. biol. Chem. 247, 6970–6977 (1972)
Rinderknecht, J., Wilding, P., Haverback, B.J.: A new method for the determination of α-amylase. Experientia (Basel) 23, 805 (1967)
Schreurs, V.V.A.M., Swarts, H.G.P., dePont, J.J.H.H.M., Bonting, S.L.: Role of calcium in exocrine pancreatic secretion. II. Comparison of the effects of carbachol and the ionophore A 23187 on enzyme secretion and calcium movements in rabbit pancreas. Biochem. biophys. Acta (Amst.) 419, 320–330 (1976)
Selinger, Z., Eimerl, S., Savion, N., Schramm, M.: A Ca++ ionophore (A 23187) simulating hormone and neurotransmitter action in the rat parotid and pancreas glands. In: Secretory mechanisms of exocrine glands (N.A. Thorn and O.H. Petersen, eds.), pp. 68–78. Copenhagen: Munksgaard 1974
Wacker, W.E.C., Ulmer, D.D., Vallee, B.L.: Metaloenzymes and myocardial infarction. II. Malic and lactic dehydrogenase activities and zinc concentrations in serum. New Engl. J. Med. 255, 449–456 (1956)
Weisenberg, R.C.: Microtubule formation in vitro in solutions containing low calcium concentrations. Science 166, 1104–1105 (1972)
Williams, J.A.: Na+ dependence of in vitro pancreatic amylase release. Amer. J. Physiol. 229, 1023–1026 (1975)
Williams, J.A.: Effects of cytochalasin B on pancreatic acinar cell structure and secretion. Cell Tiss. Res. 179, 453–466 (1977)
Williams, J.A., Chandler, D.: Ca++ and pancreatic amylase release. Amer. J. Physiol. 228, 1729–1723 (1975)
Williams, J.A., Lee, M.: Pancreatic acinar cells: Use of a Ca++ ionophore to separate enzyme release from the earlier steps in stimulus-secretion coupling. Biochem. biophys. Res. Commun. 60, 542–548 (1974)
Williams, J.A., Lee, M.: Microtubules and pancreatic amylase release by mouse pancreas in vitro. J. Cell Biol. 71, 795–806 (1976)
Wright, D.G., Bralove, D.A. Gallin, J.I.: The differential mobilization of human neutrophil granules. Amer. J. Path. 87, 273–284 (1977)
Author information
Authors and Affiliations
Additional information
Supported by grants from the NIH (GM 19998) and the Cystic Fibrosis Foundation
I am indebted to Drs. Douglas Chandler and John Heuser for discussion and advice and to M. Lee and E. Roach for technical assistance
Rights and permissions
About this article
Cite this article
Williams, J.A. The effect of the ionophore A23187 on amylase release, cellular integrity and ultrastructure of mouse pancreatic acini. Cell Tissue Res. 186, 287–295 (1978). https://doi.org/10.1007/BF00225538
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00225538