INHIBITION OF SODIUM-DEPENDENT UPTAKE PROCESSES IN PURIFIED RAT-BRAINSYNAPTOSOMES BY LOPHOZOZYMUS PICTOR TOXIN AND PALYTOXIN

To get an insight into the mechanism of neurotoxicity exhibited by Lop hozozymus pictor toxin (LPTX) and the toxin isolated from P. caribaeor um (C-PTX) studies were carried out on the effect of these toxins on t he uptake of selected substrates (neurotransmitters, amino acids and g lucose) in isolated nerve endings. The toxins were found to inhibit th e uptake of gamma-aminobutyric acid (GABA), noradrenaline, choline, L- leucine and 2-deoxy-D-glucose in rat brain synaptosomes. LPTX- or C-PT X-induced inhibition of synaptosomal uptake was reduced in the absence of Na+ in the assay medium. Synaptosomes exposed to LPTX and C-PTX re lease K+ in a dose-dependent manner. Ouabain, a selective inhibitor of the plasma membrane Na+, K+-ATPase could inhibit LPTX- and C-PTX-indu ced K+ efflux from synaptosomes and alleviate the toxin-induced inhibi tion of synaptosomal GABA uptake. It appears that the induction of ion ic flux is the primary cause of toxicity by these toxins leading to th e inhibition of Na+-dependent uptake processes in synaptosomes. The an tagonistic action of ouabain suggests the involvement of the membrane sodium pump in the development of cytotoxicity. (C) 1996 Elsevier Scie nce Ltd.