Interactions of the neurotoxic complex from the venom of the false horned viper (Pseudocerastes fieldi) with rat striatal synaptosomes.
The very high lethal potency of the neurotoxic complex (Cb) from the venom of Pseudocerastes fieldi following direct administration into the lateral ventricle of the brain, as compared with potency following i.v. administration, suggests that the toxin acts on the central nervous system. Rat striatal synaptosomes were selected to study interactions of the toxin with nerve endings. CbII, the toxic phospholipase A2 component of the toxin, as well as the reconstituted complex (CbI + CbII), inhibited the high affinity choline transport into synaptosomes. Fifty per cent inhibition was obtained at 10 nM CbII after 20 min preincubation of the synaptosomes at 37 degrees C. Choline uptake was inhibited under conditions of minimal leakage of lactate dehydrogenase and probably very low phospholipase A2 activity (in the absence of Ca2+ with Sr2+ or with EGTA). The inhibition of choline uptake was irreversible and was evident after a short preincubation at 0 degrees C. CbII also enhanced the release of acetylcholine from synaptosomes preloaded with labelled choline, but this effect was markedly reduced in the presence of the acidic component (CbI) of the complex. Binding of 125I-CbII could be demonstrated with synaptosomes and with erythrocytes, however, the reconstituted complex (CbI + CbII) was bound only by the synaptosomes, though less effectively than free 125I-CbII. An increased specific binding was evident with purified synaptosomes as compared with a crude preparation. These results support the notion that the non-toxic subunit increases the specificity of the toxic phospholipase A2.
D000818:Animals; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D010741:Phospholipases A / Q000633:toxicity; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014757:Viper Venoms / Q000633:toxicity*
D009498:Neurotoxins; D014757:Viper Venoms; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline