Effects of vinca alkaloids on uptakes of amino acids by rat brain synaptosomes

Abstract

Synaptosomal uptakes of a number of amino acids were strongly inhibited by vinblastine (I 50 = 30–50 μM). Vincristine was a less effective inhibitor and colchicine had virtually no effect. The inhibitory effects of vinblastine on uptakes of alanine, leucine and serine were modified by cations and by nucleotides. The degree of inhibition was reduced by Mg 2+ Ca 2+ and Na +; nucleotides antagonized the inhibitory effect of vinblastine but this effect required the presence of divalent cations. The inhibitory effects of vinblastine were almost abolished when the incubations were carried out at 5° instead of 37°. The efflux of amino acids from synaptosomal particles was retarded by vinblastine; this effect could be observed at a concentration as low as 15μM. By analogy with the effects of vinca alkaloids on biological processes in other tissues, our present results suggest that neurotubular protein participates in the initial rapid uptake and the subsequent efflux of amino acids in synaptosomal fractions.