Pancreatic acinar cell function: measurement of intracellular ions and pH and their relation to secretion.

1. Isolated mouse pancreatic acini were used to investigate the effect of secretagogues on acinar cellular electrolytes and cell pH. The effect of changes in the acid-base status of the incubation medium on acinar cellular electrolytes, cell pH and amylase release were also studied. 2. Carbachol at concentrations of 10(-6) or 10(-5) M was without any effect on the intracellular concentrations of total Na+, Na+ exchangeable with 22Na+, K+ and Cl-, and did not influence cell pH as determined by the DMO method. 3. Changes in pHe achieved by varying the HCO3- concentrations at constant CO2, varying the CO2 concentration at constant HCO3- or by titration of a HCO3-/CO2 free HEPES buffered medium did not influence intracellular electrolyte values. 4. pHi changed linearly with pHe by about 1.2 units/pHe unit change over the pHe range of 7.7--6.5. pHi, however, did not change in response to a change in the CO2 tension when the HCO3- concentration was adjusted to keep pHe at 7.4. 5. Lowering pHe below 7.1 inhibited carbachol and CCK8-stimulated amylase release. By contrast a decrease of pHe to 6.8 was without significant effect on basal and secretagogue increased 45Ca2+ efflux from pancreatic acini. 6. In conclusion the pH sensitivity of amylase release by acinar cells is probably related to changes in pHi. Since Ca2+ mobilization is not affected, the pH sensitive step is probably in the mechanism by which Ca2+ activates the release of zymogen granules contents by exocytosis.