Datensatz

Zusammenfassung

Evidence suggests that cholecystokinin-octapeptide (CCK-8)-induced activation of a Cl⁻ conductance in the membrane of zymogen granules (ZG) is closely related to pancreatic enzyme secretion [1,2,3]. Following stimulation of isolated pancreatic acinar cells with increasing concentrations of CCK-8, the Cl⁻ conductance in the ZG from these acini increased, reached a maximum of 40±7 % above basal Cl⁻ conductance at 10⁻¹² M CCK-8, and then decreased at CCK-8 concentrations higher than 10⁻⁹ M to a level comparable to the basal Cl⁻ conductance. We had interpreted the inhibitory action of high CCK-8 concentrations to be due to the generation of high concentrations of diacylglycerol and/or its metabolites by an “overstimulation” of phospholipase C at supramaximal CCK-8 concentrations [1]. We now show that EGF abolishes the downstroke of the dose response curve for CCK-8-induced ZG Cl⁻ conductance and shifts the stimulatory response to higher CCK-8 concentrations. Similarly in a nominally “Ca²⁺-free buffer” (free [Ca²⁺] ∼0.2 nM), stimulated Cl⁻ conductance at 10⁻¹² M CCK-8 is nearly abolished and the decreased Cl⁻ conductance at 10⁻⁸ M CCK-8 is increased to the level of maximal stimulation at 10⁻¹² M CCK-8. We conclude that both EGF and low [Ca²⁺] affect CCK-8-induced ZG Cl⁻ conductance by decreasing phospholipase C activity.