Effects of epidermal growth factor and calcium omission on cholecystokinin-stimulated Cl- conductance in rat pancreatic zymogen granules.
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. 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. 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 "Ca(2+)-free buffer" (free [Ca2+] approximately 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.
Piiper
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A
Max-Planck-Institut für Biopyhsik, Frankfurt am Main, FRG.
Pröfrock
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A
Schulz
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I
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004792:Enzyme Precursors / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology / Q000648:ultrastructure*; D051381:Rats; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D002712:Chlorides; D004792:Enzyme Precursors; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases; D012844:Sincalide; D002118:Calcium