Inhibition of intracellular protein transport in the mouse exocrine pancreas induced by vinblastine.

The effect of vinblastine on the intracellular transport of newly synthesized protein in the mouse exocrine pancreas in vivo was studied by electron microscopic autoradiography after administration of 3H-leucine. Vinblastine (1.1 mumole/mouse; i.v. injection) was in general given 1 h before radioleucine and 2-4 h before fixation of the pancreas by perfusion with glutaraldehyde. Vinblastine causes the disappearance of microtubules, mainly present in controls in the apical portion of the acinar cell. After injection of vinblastine, zymogen granules from clusters located throughout the cell but often associated with Golgi areas. The latter are enlarged mainly due to the accumulation of small vesicles. In addition, Golgi areas are displaced, most often in an apical direction. Electron microscopic autoradiography demonstrated that vinblastine delays the appearance of labeled protein in zymogen granules; even 2 h after injection of radioleucine the majority of silver grains is located over the rough endoplasmic reticulum while very few grains are related to zymogen granules. This finding might be related to the structural changes of the Golgi areas observed. Although intracellular migration of protein is retarded, zymogen granules are formed. However, many of the labeled granules are found in peculiar locations, often distant from the acinar lumen. The present study suggests that vinblastine, possibly due to its effect on microtubules, influences both the formation and the translocation of zymogen granules.