Phorbol esters and A23187 regulate Na+-K+-pump activity in pancreatic acinar cells.
To clarify the subcellular mechanisms that mediate stimulation of Na+-K+-pump activity in pancreatic acinar cells by cholinergic agonists, we examined the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 on [3H]ouabain binding to dispersed guinea pig pancreatic acinar cells under conditions in which binding reflects the average rate of pump cycling. The phorbol ester more than doubled Na+-K+-pump activity as did the diacylglycerol analogue, 1-oleoyl-2-acetolyl-sn-3-glycerol. A23187 increased pump activity by a maximum of 31% at 0.3 microM but was progressively inhibitory at higher concentrations. The stimulatory effects of TPA and A23187 were additive, although either secretagogue elicited a less than additive response when added together with a maximally effective concentration of the cholinergic agonist, carbachol. Removal of extracellular Ca2+ had little effect on the pump response to TPA and did not reduce the maximal effect of A23187 but abolished the inhibitory effect seen at high ionophore concentrations in Ca2+-containing medium. These results indicate that both Ca2+ and protein kinase c are involved in regulating Na+-K+-pump activity in the pancreatic acinar cell.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D010042:Ouabain / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D012633:Secretin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D012633:Secretin; D000001:Calcimycin; D010042:Ouabain; D000255:Adenosine Triphosphate; D002217:Carbachol; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium