Berger Z, Pap A, Ungi I, Varró V
First Department of Medicine, University Medical School, Szeged, Hungary.
Int J Pancreatol. 1986 Oct;1(3-4):279-89. doi: 10.1007/BF02795253.
In anesthetized rats, a marked decrease in CCK-OP activity and, to a far lesser extent, in the pancreatic secretory effect of CCK-33 were found after portal administration, compared to the femoral route. Changes in the biological activity of CCK-OP were further investigated after 30 min incubation with different subcellular liver fractions (1000 X g, 12,000 X g, microsomal fraction with or without NADPH). All the subcellular liver fractions caused an approximately 70% decrease in the CCK-effect, as calculated from dose-response relationships. The inactivation of CCK-OP after incubation with microsomal fractions of thioacetamide (TAA)-induced cirrhotic liver did not differ from that of control rats. The CCK-OP dose-response curves were similar in cirrhotic and control rats, but the pancreatic secretion was sustained to a greater extent and the inhibitory effect of supramaximal stimulation was delayed in cirrhotic rats. It was concluded that CCK-OP can be inactivated by liver proteins present in microsomal fractions, by a NADPH-independent mechanism. This inactivation did not diminish in liver cirrhosis. There were no changes in CCK-OP elimination in cirrhotic rats in vivo, thus pancreatic hypertrophy in experimental cirrhosis must be explained by other mechanisms.
在麻醉大鼠中，与经股动脉给药相比，门静脉给药后发现胆囊收缩素八肽（CCK-OP）活性显著降低，而CCK-33的胰腺分泌作用降低程度则小得多。在用不同亚细胞肝组分（1000×g、12000×g、含或不含NADPH的微粒体组分）孵育30分钟后，进一步研究了CCK-OP的生物活性变化。根据剂量反应关系计算，所有亚细胞肝组分均使CCK效应降低约70%。硫代乙酰胺（TAA）诱导的肝硬化肝微粒体组分孵育后CCK-OP的失活与对照大鼠无差异。CCK-OP剂量反应曲线在肝硬化大鼠和对照大鼠中相似，但肝硬化大鼠的胰腺分泌持续时间更长，超最大刺激的抑制作用延迟。得出的结论是，CCK-OP可被微粒体组分中存在的肝脏蛋白通过不依赖NADPH的机制失活。这种失活在肝硬化中并未减弱。肝硬化大鼠体内CCK-OP的消除没有变化，因此实验性肝硬化中的胰腺肥大必须用其他机制来解释。
