Smith G D, Christensen J R, Rideout J M, Peters T J
Division of Clinical Cell Biology, Medical Research Council Clinical Research Centre, Harrow, Middlesex, England.
Eur J Biochem. 1989 May 1;181(2):287-94. doi: 10.1111/j.1432-1033.1989.tb14723.x.
The effect of selected weak bases on the subcellular distribution and processing of internalized insulin by the liver has been studied. The effect of these bases on both the degradation products formed and on the kinetics of degradation have also been studied. 1. Methylamine, ammonium chloride and dansyl cadaverine but not chloroquine reduce the total amount of insulin endocytosed. 2. Ammonium chloride, dansyl cadaverine and chloroquine but not methylamine inhibit subsequent degradation and/or translocation of degradation products. 3. None of the weak bases changed the species of the degradation products found within the endocytic vesicles. 4. Kinetic analysis of intravesicular degradation indicates that dissociation from the receptor is the rate-limiting process in degradation. 5. Chloroquine and dansyl cadaverine but not methylamine or ammonium chloride showed specific inhibition of insulin degradation in isolated endocytic vesicles. 6. The effect of chloroquine and dansyl cadaverine on the kinetics of degradation suggest that they are acting by switching the receptor into a tight-binding conformation thereby slowing dissociation.
研究了所选弱碱对肝脏内化胰岛素的亚细胞分布及处理的影响。还研究了这些碱对形成的降解产物以及降解动力学的影响。1. 甲胺、氯化铵和丹磺酰尸胺而非氯喹会减少内吞的胰岛素总量。2. 氯化铵、丹磺酰尸胺和氯喹而非甲胺会抑制后续降解和/或降解产物的转运。3. 没有一种弱碱改变在内吞小泡中发现的降解产物种类。4. 小泡内降解的动力学分析表明，从受体上解离是降解中的限速过程。5. 氯喹和丹磺酰尸胺而非甲胺或氯化铵对分离的内吞小泡中的胰岛素降解有特异性抑制作用。6. 氯喹和丹磺酰尸胺对降解动力学的影响表明，它们的作用方式是将受体转变为紧密结合构象，从而减缓解离。
