J Neurobiol. 1978 Nov;9(6):453-63.
Effect of experimental colchicine encephalopathy on brain protein synthesis and tubulin metabolism.

McMartin DN, Schedlbauer LM.

Colchicine blocks axoplasmic flow and produces neurofibrillary degeneration. Brain slices from mice injected intracerebrally with colchicine incorporated more [14C]leucine into protein and had a decreased uptake of [14C]leucine into the perchloric acid-soluble pool than did their controls. Brain RNA content was decreased and free leucine increased by colchicine-induced encephalopathy. The specific activities of proteins from subcellular fractions of colchicine-injected brain were increased in the nuclear fraction, the 100,000-g supernatant, and its vinblastine-precipitable tubulin. The ratio of the specific activity of the crude mitochondrial fraction to that of the total homogenate was decreased, as would be consistent with impaired movement of newly labeled protein into synaptosomes. Colchicine-injected brain extracts contained one or more cytosol fractions that stimulated ribosomal incorporation of [14C]leucine into protein in a cell-free system. Colchicine-binding-activity measurements indicated loss of soluble and particulate tubulin in colchicine-injected brains; the decrease of soluble tubulin was verified by its selective precipitation with vinblastine. Colchicine encephalopathy did not affect the rate of spontaneous breakdown of in vitro colchicine binding activity. Similarities of colchicine encephalopathy to the neuron's response to axonal damage suggest that colchicine-induced increase in protein synthesis may, in part, reflect a neuronal response to blockage of neuroplasmic transport.


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J Neuropathol Exp Neurol. 1979 May;38(3):286-99.
Evidence for an intraaxonal transport of fixed and street rabies virus.

Tsiang H.

Colchicine was used to inhibit axonal transport and to demonstrate that rabies virus spread from the peripheral inoculation site to the CNS by the retrograde axoplasmic flow. Colchicine was applied by the mean of elastomer implants around the sciatic nerve of young rats in order to obtain higher local concentrations of the drug. This procedure avoided the systemic effects of colchicine encountered with the usual treatment. To confirm the efficiency of the axoplasmic flow inhibition by colchicine, 125I-tetanus toxin was used as a marker. Uptake of colchicine by the sciatic nerve was monitored by the use of 3H-labelled colchicine. Interruption of the retrograde axoplasmic flow resulted in prevention of fixed and street rabies virus propagation. Moreover, the centrifugal spread of rabies could be inhibited using this experimental procedure.


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Brain Res. 1979 Aug 10;171(3):415-24.
The role of axonal transport in the regulation of enzyme activity in sympathetic ganglia of adult rats.

Kessler JA, Black IB.

The relationship of perikaryal and presynaptic enzyme activity to axonal transport was studied in adult sympathetic neurons in the rat superior cervical ganglion (SCG). Surgical axotomy or local colchicine application to the postganglionic nerves resulted in a significant decrease in ganglionic tyrosine hydroxylase (T-OH) activity without a significant alteration in choline acetyltransferase activity. Colchicine did not appear to block axonal impulse conduction since pupillary and eyelid function remained normal. Consequently, the reduced T-OH activity resulted from alteration of other axonal functions. Axotomy or colchicine application decreased T-OH activity in decentralized ganglia, suggesting that the depression of perikaryal T-OH was not secondary to altered orthograde transsynaptic interactions. Colchicine did not prevent transsynaptic induction of T-OH by reserpine, suggesting that axonal transport is not necessary for enzyme induction. Nerve growth factor (NGF) treatment partially prevented the effects of colchicine application. It is concluded that in adult sympathetic neurons both orthograde transsynaptic mechanisms and the retrograde transport of NGF normally govern perikaryal T-OH activity.


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J Membr Biol. 1978 May 3;40(3):237-50.
Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. II. Colchicine binding properties of toad bladder epithelial cell tubulin.

Wilson L, Taylor A.

Colchicine, podophyllotoxin and vinblastine have been found to inhibit the action of vasopressin on water movement in the toad urinary bladder. Tubulin is the major colchicine binding component of toad bladder epithelial cells, accounting for approximately 3.3% of the total cell protein. More than 99% of the tubulin is found in the soluble fraction after sonication, the remainder is in the particulate fraction. Similar to the characteristics of the binding of colchicine to tubulins from other sources, the binding of colchicine to toad bladder tubulin is temperature- and time-dependent, is inhibited competitively by podophyllotoxin (Ki= 5.5 x 10(-7)m), and has a binding constant of 1 X 10(6) liters/mole at 37 degrees. Binding activity decays according to first-order kinetics and is stabilized by vinblastine. The characteristics of the interactions of colchicine and podophyllotoxin with epithelial cell tubulin in vitro closely parallel the ability of these drugs to inhibit the response to vasopressin in vivo. These results, coupled with those of functional and morphological studies, support the view that the ability of these drugs to affect vasopressin-induced water movement across toad bladder epithelial cells is related to the depolymerization of cytoplasmic microtubules.


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