Bennett G, Carlet E, Wild G, Parsons S
Am J Anat. 1984 Aug;170(4):545-66. doi: 10.1002/aja.1001700404.
In the first paper of this series (Bennett et al., 1984), light-microscope radioautographic studies showed that colchicine or vinblastine inhibited intracellular migration of glycoproteins out of the Golgi region in a variety of cell types. In the present work, the effects of these drugs on migration of membrane glycoproteins have been examined at the ultrastructural level in duodenal villous columnar cells and hepatocytes. Young (40 gm) rats were given a single intravenous injection of colchicine (4.0 mg) or vinblastine (2.0 mg). At 10 min after colchicine and 30 min after vinblastine administration, the rats were injected with 3H-fucose. Control rats received 3H-fucose only. All rats were sacrificed 90 min after 3H-fucose injection and their tissues processed for radioautography. In duodenal villous columnar cells, 3H-fucose labeling of the apical plasma membrane was reduced by 51% after colchicine and by 67% after vinblastine treatment; but there was little change in labeling of the lateral plasma membrane. Labeling of the Golgi apparatus increased. This suggests that labeled glycoproteins destined for the apical plasma membrane were inhibited from leaving the Golgi region, while migration to the lateral plasma membrane was not impaired. In hepatocytes, labeling of the sinusoidal plasma membrane was reduced by 83% after colchicine and by 85% after vinblastine treatment. Labeling of the lateral plasma membrane also decreased, although not so dramatically. Labeling of the Golgi apparatus and neighboring secretory vesicles increased. This indicates that the drugs inhibited migration of membrane glycoproteins from the Golgi region to the various portions of the plasma membrane. Accumulation of secretory vesicles at the sinusoidal front suggests that exocytosis may also have been partially inhibited. In both cell types, microtubules almost completely disappeared after drug treatment. Microtubules may, therefore, be necessary for intracellular transport of membrane glycoproteins, although the possibility of a direct action of these drugs on Golgi or plasma membranes must also be considered.
在本系列的第一篇论文中（贝内特等人，1984年），光学显微镜放射自显影研究表明，秋水仙碱或长春花碱在多种细胞类型中抑制了糖蛋白从高尔基体区域向细胞内的迁移。在本研究中，已在十二指肠绒毛柱状细胞和肝细胞的超微结构水平上研究了这些药物对膜糖蛋白迁移的影响。给40克重的幼鼠静脉内单次注射秋水仙碱（4.0毫克）或长春花碱（2.0毫克）。在注射秋水仙碱10分钟后和注射长春花碱30分钟后，给大鼠注射3H-岩藻糖。对照大鼠仅接受3H-岩藻糖。在注射3H-岩藻糖90分钟后处死所有大鼠，并对其组织进行放射自显影处理。在十二指肠绒毛柱状细胞中，秋水仙碱处理后顶端质膜的3H-岩藻糖标记减少了51%，长春花碱处理后减少了67%；但侧质膜的标记变化不大。高尔基体的标记增加。这表明，注定要到达顶端质膜的标记糖蛋白被抑制离开高尔基体区域，而向侧质膜的迁移未受损害。在肝细胞中，秋水仙碱处理后窦状质膜的标记减少了83%，长春花碱处理后减少了85%。侧质膜的标记也减少了，尽管不那么显著。高尔基体和相邻分泌小泡的标记增加。这表明药物抑制了膜糖蛋白从高尔基体区域向质膜各部分的迁移。分泌小泡在窦状前沿的积累表明胞吐作用也可能受到了部分抑制。在两种细胞类型中，药物处理后微管几乎完全消失。因此，微管可能是膜糖蛋白细胞内运输所必需的，尽管也必须考虑这些药物对高尔基体或质膜的直接作用的可能性。
