Inhibition of L-glutamate and GABA synaptosome uptake by crotoxin, the major neurotoxin from Crotalus durissus terrificus venom



Document title: Inhibition of L-glutamate and GABA synaptosome uptake by crotoxin, the major neurotoxin from Crotalus durissus terrificus venom
Journal: The journal of venomous animals and toxins including tropical diseases
Database: PERIÓDICA
System number: 000298814
ISSN: 1678-9199
Authors: 1
2
3
4
Institutions: 1Universidade de Sao Paulo, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, Sao Paulo. Brasil
2Universidade de Ribeirao Preto, Unidade de Biotecnologia, Ribeirao Preto, Sao Paulo. Brasil
3Universidade de Sao Paulo, Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Sao Paulo. Brasil
4Oregon Health Sciences University, Vollum Institute, Portland, Oregon. Estados Unidos de América
Year:
Volumen: 10
Number: 3
Pages: 260-279
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract This paper describes a brief study on the crotoxin mechanism of action, regarding the transport of GABA and L-glutamate in rats cortico-cerebral synaptosomes and in heterologous systems, such as COS-7 cells expressing gabaergic transporters, and C6 glioma cells and Xenopus oocytes expressing glutamatergic transporters. Crotoxin concentrations over 1 µM caused an inhibitory effect of ³H-L-glutamate and ³H-GABA, and reversibly inhibited L-glutamate uptake by C6 glioma cells. When COS-7 cells were assayed, no inhibition of the ³H-GABA transport could be evidenced. Crotoxin kept its inhibitory effect on neurotransmitters uptake even when Ca2+ ions were removed from the medium, therefore, independently of its PLA2 activity. In addition, high concentrations (2 mM) of BPB did not avoid the action of crotoxin on the neurotransmitters uptake. Crotoxin also inhibited ³H-L-glutamate, independently on Na+ channel blockade by TTX. In addition, an evaluation of the lactic dehydrogenase activity indicated that uptake inhibition does not involve a hydrolytic action of crotoxin upon the membrane. We may also suggest that crotoxin acts, at least partially, altering the electrogenic equilibrium, as evidenced by confocal microscopy, when a fluorescent probe was used to verify cell permeability on C6 glioma cells in presence of crotoxin
Disciplines: Biología
Keyword: Reptiles,
Bioquímica,
Veneno de víbora,
Crotoxina,
Mecanismo de acción,
Glutamato,
GABA,
Crotalus durissus terrificus,
Viperidae
Keyword: Biology,
Reptiles,
Biochemistry,
Snake venom,
Crotoxin,
Action mechanism,
Glutamate,
GABA,
Crotalus durissus terrificus,
Viperidae
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