Effects of colchicine on the intraneuronal transport of secretory material prior to the axon: a morphofunctional study in hypothalamic neurosecretory neurons of the rat.

The effects of colchicine on neurosecretory neurons of the rat hypothalamus were studied by immunocytochemistry, high-resolution radioautography, and conventional electron microscopy. In control rats, intraneuronal immunocytochemical labeling of vasopressin, oxytocin and somatostatin occurred essentially in the Golgi apparatus, the neurosecretory granules and to a lesser extent, the endoplasmic reticulum. These immunostaining patterns were dramatically modified 24 h after the administration of colchicine: immunoreactive peptides were located in granular or tubular structures accumulated at the periphery of the perikarya, but the Golgi stacks were not immunostained. Two h after the administration of tritiated leucine, quantitative analysis of radioautographic labeling of supraoptic perikarya revealed large amounts of radioactive protein in the Golgi saccules of neurosecretory neurons in control rats, but in the neurons of colchicine-treated rats, radioautographic labeling was mainly located in granular structures accumulated at the periphery of the perikarya, with no significant labeling on the Golgi stacks. Lastly, 3 noteworthy effects of colchicine on the ultrastructural morphological features of these neurosecretory neurons consisted in: (1) a dramatic disorganization of the Golgi complexes, (2) an accumulation of electron-dense proteic material within the lumen of cisternae of both the rough and smooth endoplasmic reticulum and, (3) a marked depolymerization of perikaryal microtubules, specifically those associated with the Golgi stacks. Taken together, these data do not fit the prevailing concept that the colchicine-induced accumulation of secretory material within the perikarya of neurosecretory neurons essentially results from the blockade of axoplasmic transport mechanisms. Instead, they support the idea that the effects of colchicine are related to the inhibition of the intraneuronal transport of newly synthesized secretory material from the endoplasmic reticulum to the Golgi apparatus, suggesting that the microtubules associated with the Golgi stacks are possible sites of colchicine action.