Inhibition of sodium-dependent uptake processes in purified rat brain synaptosomes by Lophozozymus pictor toxin and palytoxin.
To get an insight into the mechanism of neurotoxicity exhibited by Lophozozymus pictor toxin (LPTX) and the toxin isolated from P.caribaeorum (C-PTX) studies were carried out on the effect of these toxins on the uptake of selected substrates (neurotransmitters, amino acids and glucose) in isolated nerve endings. The toxins were found to inhibit the uptake of gamma-aminobutyric acid (GABA), noradrenaline, choline, L-leucine and 2-deoxy-D-glucose in rat brain synaptosomes. LPTX- or C-PTX-induced inhibition of synaptosomal uptake was reduced in the absence of Na+ in the assay medium. Synaptosomes exposed to LPTX and C-PTX release K+ in a dose-dependent manner. Ouabain, a selective inhibitor of the plasma membrane Na+, K(+)-ATPase could inhibit LPTX- and C-PTX-induced K+ efflux from synaptosomes and alleviate the toxin-induced inhibition of synaptosomal GABA uptake. It appears that the induction of ionic flux is the primary cause of toxicity by these toxins leading to the inhibition of Na(+)-dependent uptake processes in synaptosomes. The antagonistic action of ouabain suggests the involvement of the membrane sodium pump in the development of cytotoxicity.
Lau
C O
CO
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Ng
F H
FH
Khoo
H E
HE
Yuen
R
R
Tan
C H
CH
D000178:Acrylamides / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003386:Brachyura; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003064:Cnidarian Venoms; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000095702:Polyether Toxins
D000178:Acrylamides; D000596:Amino Acids; D002794:Choline; D003064:Cnidarian Venoms; D005947:Glucose; D018377:Neurotransmitter Agents; D009638:Norepinephrine; D010042:Ouabain; D011188:Potassium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005680:gamma-Aminobutyric Acid; C010272:palytoxin; D000095702:Polyether Toxins