Effects of Colchicine, Vinblastine and Vincristine on Degeneration Transmitter Release after Sympathetic Denervation Studied in the Conscious Rat

Abstract

AbstractThe effect of the mitosis inhibitors colchicine, vinblastine and vincristine on the time course of the degeneration contraction of the sympathetically innervated periorbital smooth muscle was studied in conscious rats. In conformity with earlier findings with colchicine, single s.c. doses of vinblastine (2–4 mg/kg) or vincristine (1–2 mg/kg) given at the time of axotomy delayed the start of the degeneration contraction, i.e. the leakage of sympathetic transmitter from the degenerating nerve endings. The significance for the delaying effect of the time interval between axotomy and injection of colchicine was studied in some detail. The delaying effect declined gradually with increasing time interval between denervation and injection. Colchicine given later than 4–6 h after axotomy did not delay. In view of this finding and the fact that the mitosis inhibitors used are known to inhibit the intra‐axonal microtubular transport of different nerve constituents it is proposed that the drugs postpone the degeneration transmitter release by slowing down the rate by which an “axotomy information” is transported distally along the neuron. The “axotomy information”, probably linked to some axotomy‐induced change in intra‐axonal structures related to the microtubules, seems to be transported at a rate of about 4 mm per hr. Local treatment of the decentralized superior cervical ganglion with colchicine or vinblastine induced a “degeneration” contraction probably due to a complete inhibition of the flow of some vital matter to the nerve endings.