Lewin M B, Sankaran H, Deveney C W, Wong A, Wendland M F, Geokas M C
Biochem Pharmacol. 1984 Oct 15;33(20):3225-9. doi: 10.1016/0006-2952(84)90081-9.
Cholecystokinin octapeptide (CCK8)-stimulated amylase release in isolated rat pancreatic acini was inhibited over 30% by 600 mM ethanol. The configuration of the dose-response curve for CCK8, however, in the presence of ethanol was similar to that of the control. Amylase release elicited by maximal concentrations of CCK8 (300 pM) was inhibited by increasing concentrations of ethanol (0.3 to 1.3 M), and this inhibition was concentration dependent. In addition, the binding of [125I]CCK33 to specific membrane receptors on acini was inhibited by ethanol in a dose-dependent manner. A positive correlation between the inhibitory effects of ethanol on CCK binding and CCK-induced amylase release was observed. Furthermore, these inhibitory effects of ethanol were reversible. Basal amylase release, however, was increased 20-50% by ethanol between the concentrations of 0.3 and 1.3 M; higher concentrations caused a leakage of amylase from the acini both in the absence and presence of 300 pM CCK8. This is confirmed by 51Cr release from prelabeled acini which revealed no significant damage to acinar cell membrane between 0.3 and 1.6 M ethanol, but significant damage to acini at higher concentrations. These data suggest that the 600 mM ethanol-induced inhibition of CCK action in acini is due to reversible perturbation of the acinar cell membrane.
在分离的大鼠胰腺腺泡中，600 mM乙醇可使胆囊收缩素八肽（CCK8）刺激的淀粉酶释放受到超过30%的抑制。然而，在乙醇存在的情况下，CCK8剂量-反应曲线的形态与对照组相似。最大浓度（300 pM）的CCK8引发的淀粉酶释放受到浓度不断增加的乙醇（0.3至1.3 M）的抑制，且这种抑制呈浓度依赖性。此外，[125I]CCK33与腺泡上特定膜受体的结合也受到乙醇的剂量依赖性抑制。观察到乙醇对CCK结合及CCK诱导的淀粉酶释放的抑制作用之间呈正相关。此外，乙醇的这些抑制作用是可逆的。然而，在0.3至1.3 M的浓度范围内，乙醇可使基础淀粉酶释放增加20%至50%；在不存在和存在300 pM CCK8的情况下，更高浓度的乙醇都会导致淀粉酶从腺泡中泄漏。预先标记的腺泡释放51Cr证实了这一点，结果显示在0.3至1.6 M乙醇浓度范围内，腺泡细胞膜未受到明显损伤，但在更高浓度下腺泡受到明显损伤。这些数据表明，600 mM乙醇诱导的对腺泡中CCK作用的抑制是由于腺泡细胞膜的可逆性扰动。
