J Cell Biol. 1976 Oct;71(1):182-95.
Effect of colchicine on rat mast cells.

Lagunoff D, Chi EY.

In the mast cell, a well-developed array of microtubules is centered around the centrioles. Complete loss of microtubules is observed when mast cells are treated with 10(-5) M colchicine for 4 h at 37 degrees C. The loss of ultrastructurally evident microtubules is associated with a marked change in the shape of mast cells from spheroids to highly irregular, frequently elongated forms with eccentric nuclei. In colchicine-treated cells the association of nucleus, Golgi apparatus, and centrioles is also lost. Mast cells exposed to 10(-5) M colchicine for 4 h at 37 degrees C retain 80% of their capacity to release histamine when stimulated by polymyxin B. Exocytosis is evident in stimulated cells pretreated with colchicine and lacking identifiable microtubules. When the conditions of exposure of mast cells to colchicine are varied with respect to the concentration of colchicine, the length of exposure, and the temperature of exposure, dissociation between deformation of cell shape and inhibition of histamine secretion is observed. These observations indicate that microtubules are not essential for mast cell histamine release and bring into question the assumption that the inhibitory effect of colchicine on mast cell secretion depends on interference with microtubule integrity.


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J Physiol. 1977 Jan;264(3):725-49.
The effects of nerve section and of colchicine treatment on the density of mechanosensory nerve endings in salamander skin.

Cooper E, Diamond J, Turner C.

We have shown that when one of the spinal nerves supplying the salamander hind limb is cut or treated with colchicine, the fields of the remaining nerves enlarge in area; whereas nerve section produces Wallerian degeneration, the colchicine-treated nerves conducted action potentials normally and their peripheral fields remained unchanged in area (Aguilar, Bisby, Cooper & Diamond, 1973). Since colchicine-treatment reduced neuronal transport, and nerve-section eliminated it, we proposed that nerve sprouting is regulated by factors normally conveyed to the endings by axoplasmic transport. 1. We have now investigated the effects of colchicine on the thresholds and distribution of individual mechanosensory endings in the skin. If reduction of neuronal transport were enough to cause the threshold to be increased to the point of total unresponsiveness, then this could be a sign of an early stage of degernation in those terminals. It could then be hypothesized that products of degeneration were providing a stimulus for adjacent nerves to sprout. 2. Quantitative physiological studies of the effects of colchicine doses known to interfere with fast axoplasmic transport, indicate that in some experiments the terminal field of the treated nerve was invaded by sprouting fibres from neighbouring axons, when its own endings were unchanged in number, distribution and sensory thresholds. In other experiments the colchicine-treated nerve endings showed an increase in threshold but their function was otherwise unchanged; a similar adjacent nerve sprouting occurred. In a final group, colchicine caused total unresponsiveness of some endings of the treated nerve. 3. When a region of skin was partially denervated by nerve section, the physiological analysis indicated that the number of new mechanosensory endings which sprouted from the remaining axons exactly matched the number lost by nerve degeneration: furthermore the distribution of the endings was normal. It therefore appears that sprouting ceased when the original density of mechanosensory endings in the skin was restored. 4. The possibility that the drug induced sprouting as a consequense of a direct action on the skin is unlikely. With [3H]colchicine, we found that the accumulation of label in the skin of the untreated limb, in which sprouting did not occur, equalled that of the opposite limb. 5. The present results lend support to the original hypothesis of Aguilar et al. (1973), which proposed that collateral sprouting of intact nerves occurs when the supply of neuronally transported factors becomes inadequate to balance out the effects of a postulated target-tissue stimulus. In the Discussion other examples of collateral nerve sprouting, such as that following adjacent denervation, are shown to be explainable by this hypothesis.


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J Physiol. 1977 Feb;265(1):63-84.
The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.

Cangiano A, Fried JA.

1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff. 2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated. 3. These effects were not restricted to the EDL muscle of the colchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic. 4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side. 5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed. 6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane.


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Tsitologiia. 1976;18(6):725-30.
[Effect of various antimicrotubular drugs on the osmotic water flow through the wall of frog's urinary bladder]

[Article in Russian]

Bagrow IaIu, Gol'fand KA, Kaulin AB, Manusova NB.

The action of antimicrotubular drugs (colchicine, vinblastine and copper) on the osmotic water flow through the wall of the urinary bladder of Rana temporaria has been studied. The osmotic gradient was made by five- or tenfold dilution of the internal Ringer solution. The water flow was estimated gravimetrically. The water flow was induced by pituitrin (50 milliunits/ml), cyclic AMP (cAMP, 0.5-10(-3) M) and nystatine (3.5-10(-5) M). Pituitrin and cAMP and all the antimicrotubular drugs were added from the serosal surface of the bladder. Nystatine was introduced with the help of a fixed polyethylene tube. Preincubation with colchicine lasted 4 hours and that with vinblastine and copper (CuSO4), 1 hour. The drug concentrations varied between 10(-5)--10(-4) M. All the drugs studied showed a significant inhibitory effect toward pituitrin. The action of cAMP on the water flow was seen inhibited in the presence of colchicine and copper. The nystatine induced water flow was supressed by copper, colchicine being in this case inactive. A conclusion is drawn that the inhibition of cAMP formation does not cause a decreased pituitrine effect in the presence of antimicrotubular drugs. It has been assumed that the microtubules may be involved in the directed water flow within the cell.


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