title: Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P/Q calcium channels.
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.
authors.affiliation: Programa de Neurociências, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rosangela da Silva
authors.initials: Rda S
authors.lastname: Lomeo
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Paula de Faria
authors.initials: AP
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carolina Nunes
authors.initials: CN
authors.lastname: da Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: André Tunes
authors.initials: AT
authors.lastname: de Paula
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Danielle Oliveira
authors.initials: DO
authors.lastname: Costa Santos
authors.affiliation: Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Consuelo Latorre
authors.initials: CL
authors.lastname: Fortes-Dias
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Programa de Neurociências, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: melenalima@icb.ufmg.br.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
mesh_terms: D000818:Animals; D002120:Calcium Channel Agonists / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry* / Q000201:enzymology; D017839:Crotalus; D003439:Crotoxin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D017208:Rats, Wistar; D030162:Reptilian Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D003435:Crotalid Venoms; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D021122:Protein Subunits; D030162:Reptilian Proteins; D018698:Glutamic Acid; D003439:Crotoxin; D054501:Group II Phospholipases A2
keywords: Calcium channels; Crotoxin; PLA2; Synaptosomes; l-glutamate