Effect of colchicine on 45Ca and choline uptake, and acetylcholine release in rat brain synaptosomes

The effects of 1 and 10 mM colchicine on the K+-evoked release of preformed and newly synthesized acetylcholine and on the K+-depolarization-stimulated uptake of 45Ca were compared in rat brain synaptosomes. Preincubation of synaptosomes with 1 mM colchicine had little effect on transmitter release and on uptake of 45Ca; 10 mM colchicine inhibited both the release of transmitter and uptake of 45Ca by 58%. Since 1 mM colchicine has been shown to disaggregate intrasynaptosomal microtubules almost completely, but to be without effect on release of either preformed or newly synthesized acetylcholine in our experiments, it is concluded that colchicine modifies transmitter release by reducing Ca2+ influx, rather than by its postulated intracellular action on microtubule-mediated transmitter mobilization. In addition, 1 and 10 mM cholchicine significantly inhibited the high-affinity choline uptake in synaptosomes. This hemicholinium-like action of colchicine may contribute to the reduction of transmitter release.