Effects of the calcium ionophore A23187 on pancreatic acinar cell membrane potentials and amylase release.

Abstract

SUMMARY1. The effects of the Ca2+-ionophore A23187 and the non-metabolizable cholinergic agonist bethanechol on acinar cell membrane potentials and amylase release from the superfused mouse pancreas were studied.2. In the presence of extracellular Ca2+ (2.56 mM), A23187 (10-5M) and bethanechol (3 x 10-, M) caused an equal increase in the release of amylase. Both stimulants depolarized the acinar cells, A23187 by 60 mV and bethanechol by 12-3 mV.3. When Ca2+ and Mg2+ were removed from the superfusate, the ability of A23187 to increase the rate of amylase release was virtually abolished, while the effect of bethanechol remained unaltered. Similarly, in the absence of these divalent cations, A23187 did not cause depolarization of the acinar cells, while depolarization in response to bethanechol was largely normal. Consequently it is unlikely that cholinergic agonists initiate secretion by activating a Ca2+-ionophore-like mechanism in the cell membrane.4. When the concentration of Ca2+ in the medium was raised to 10 mM, as the only divalent cation present, the depolarization in response to A23187 was increased to 11-8 mV. When Mg2+ in a concentration of 10 mM was the only extracellular divalent cation, the depolarization was only 2-1 mV.5. The Ca2+ dependent, A23187-induced depolarization was abolished in the absence of Na+ (Tris substitution). Addition of Na+ to the superfusate caused an immediate depolarization.6. It is concluded that the Ca2+ dependent depolarization of pancreatic acinar cells induced by A23187 is not directly due to an increased divalent

In vitro action of bombesin on amylase secretion, membrane potential, and membrane resistance in rat and mouse pancreatic acinar cells. A comparison with other secretagogues.

“…The dose-response curves for bombesin-evoked resistance change, depolarization, and amylase secretion are very similar as they are in the case of ACh (19). Depolarization of the pancreatic acinar cell membrane by excess extracellular K does not evoke amylase secretion if atropine is present to prevent the action of ACh liberated from depolarized nerve endings (20,21). This finding does not, however, indicate that the ACh, CCK, or bombesin-evoked membrane changes are unimportant.…”

“…The quantitative similarity of the action of bombesin on the acinar cell electrophysiological properties to that of ACh therefore suggests that bombesin also causes similar transmembrane ion fluxes. The recent findings that the calcium ionophore A23187 and intracellular Ca application by micro-iontophoresis to pancreatic acinar cells induce membrane depolarization and resistance reduction (21,22) suggest that the plasma membrane Cl, Na, and K conductance changes evoked by ACh, bombesin, and CCK may be mediated by an increase in [Ca2+]i. This would explain why the equilibrium potentials for the action of all three groups of agonists acting on three different receptor sites are identical (Fig.…”

“…High extracellular K depolarizes the acinar cell membrane without changing the membrane resistance (8) whereas ACh, CCK, gastrin, pentagastrin, caerulein, and bombesin all evoke a marked reduction in acinar cell surface membrane resistance (8)(9)(10). Stimulating pancreatic amylase secretion by raising the cytosol-ionized calcium concentration without receptor activation, with the divalent cation ionophore A23187 or direct intracellular Ca2+ injection, also causes membrane resistance reduction and depolarization (21,22).…”

Stimulus-secretion coupling of renin. Role of hemodynamic and other factors.

“…4, OCTOBER 1980 The calcium ionophore A23187, which promotes calcium entry into cells (Pressman, 1973), inhibits renin secretion in the presence of extracellular calcium, presumably by increasing net calcium influx and cytoplasmic calcium (Fynn et al, 1977;Baumbach and Leyssac, 1977); the ionophore stimulates renin secretion in the absence of extracellular calcium, presumably by removing calcium from the cytoplasm. A23187 also depolarizes some cell membranes when calcium is present but not when it is absent from the extracellular fluid (Poulsen and Williams, 1977;Cochrane and Douglas, 1975).…”

Pancreatic acinar cells: effects of microionophoretic polypeptide application on membrane potential and resistance

“…This method has also been used to determine the calcium-injection null potential directly, and a value of about -16 mV was found . Increasing intracellular calcium using the calcium ionophore A23187 has also induced acinar cell depolarization (Poulsen & Williams, 1977b) in addition to raising amylase output from mouse (Poulsen & Williams, 1977b) and rat (Selinger, Eimerl, Savion & Schramm, 1974). The effect of increasing intracellular calcium appears to 313 0.…”