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Toxicon ; 85: 5-16, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24751366

ABSTRACT

Crotoxin (Crtx), the main toxin in the venom of Crotalus durissus terrificus snake, is a heterodimer with a basic subunit, CB, and an acidic subunit, CA. CB is a phospholipase A2 that depends on CA to specifically bind to the cell membrane. This toxin acts in the central nervous system (CNS) causing chronic seizure effects and other cytotoxic effects. Here, we report its action on glutamate release in rat cerebral cortex synaptosomes. Aiming at a better understanding of the mechanism of action of Crtx, calcium channel blockers were used and internalization studies were performed in cerebellar granule neurons. Our results show that Crtx induces calcium-dependent glutamate release via N and P/Q calcium channels. In addition, the CB subunit of Crtx is shown to be internalized. This internalization does not depend on the presence of CA subunit neither on the PLA2 activity of CB. A correlation between CB internalization and glutamate release remains to be established.


Subject(s)
Calcium Channel Agonists/pharmacology , Calcium Channels, N-Type/metabolism , Cerebral Cortex/drug effects , Crotalid Venoms/chemistry , Crotalus , Crotoxin/pharmacology , Synaptosomes/drug effects , Animals , Calcium Channel Agonists/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels, N-Type/chemistry , Calcium Signaling/drug effects , Cells, Cultured , Cerebral Cortex/metabolism , Crotalid Venoms/enzymology , Crotoxin/antagonists & inhibitors , Crotoxin/metabolism , Glutamic Acid/metabolism , Group II Phospholipases A2/antagonists & inhibitors , Group II Phospholipases A2/metabolism , Group II Phospholipases A2/pharmacology , Male , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/metabolism , Neurons/drug effects , Neurons/metabolism , Neurotoxins/antagonists & inhibitors , Neurotoxins/metabolism , Neurotoxins/pharmacology , Protein Subunits/antagonists & inhibitors , Protein Subunits/metabolism , Protein Subunits/pharmacology , Protein Transport/drug effects , Rats, Wistar , Reptilian Proteins/antagonists & inhibitors , Reptilian Proteins/metabolism , Reptilian Proteins/pharmacology , Synaptic Transmission/drug effects , Synaptosomes/metabolism
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