Piiper A, Pröfrock A, Schulz I
Max-Planck-Institut für Biopyhsik, Frankfurt am Main, FRG.
Biochem Biophys Res Commun. 1991 Dec 16;181(2):827-32. doi: 10.1016/0006-291x(91)91264-d.
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.
有证据表明，胆囊收缩素八肽（CCK - 8）诱导的酶原颗粒（ZG）膜中氯离子电导的激活与胰腺酶分泌密切相关。用浓度递增的CCK - 8刺激分离的胰腺腺泡细胞后，这些腺泡ZG中的氯离子电导增加，在10^(-12) M CCK - 8时达到比基础氯离子电导高40±7%的最大值，然后在高于10^(-9) M的CCK - 8浓度下下降至与基础氯离子电导相当的水平。我们曾将高浓度CCK - 8的抑制作用解释为在超最大CCK - 8浓度下磷脂酶C的“过度刺激”导致高浓度二酰基甘油和/或其代谢产物的产生。我们现在表明，表皮生长因子（EGF）消除了CCK - 8诱导的ZG氯离子电导剂量反应曲线的下降，并将刺激反应转移到更高的CCK - 8浓度。同样，在名义上的“无钙缓冲液”（游离[Ca2 +]约为0.2 nM）中，10^(-12) M CCK - 8刺激的氯离子电导几乎被消除，而10^(-8) M CCK - 8时降低的氯离子电导增加到10^(-12) M CCK - 8时的最大刺激水平。我们得出结论，EGF和低[Ca2 +]均通过降低磷脂酶C活性来影响CCK - 8诱导的ZG氯离子电导。
