Document Detail


PnTx4-3, a new insect toxin from Phoneutria nigriventer venom elicits the glutamate uptake inhibition exhibited by PhTx4 toxic fraction.
MedLine Citation:
PMID:  14757211     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several pools of neurotoxic peptides obtained from fractionated Phoneutria nigriventer venom induce different toxicological effects. One of them, PhTx4, is highly toxic towards insects and displays only a slight toxicity when injected in mice. Also, this fraction contains a class of peptides that are able to inhibit glutamate uptake in preparations of mammalian central nervous systems (CNS). In this work a new toxin called PnTx4-3 was isolated from the PhTx4 fraction by reverse phase and anion exchange steps using high performance liquid chromatography (HPLC). Edman sequencing of PnTx4-3 revealed that it was a polypeptide of 48 amino acid residues, containing 10 cysteines cross-linked by five disulfide bridges. The molecular mass measured by ES-Q-TOF mass spectrometry was 5199.49+/-0.64 Da, which is very close to the calculated mass from amino acid sequence (5199.99 Da). This toxin induces immediate excitatory effects when injected intrathoracically in house flies and cockroaches. Intracerebroventricular injections of 30 microg of PnTx4-3 in mice resulted in no apparent signs of intoxication. In order to make an orthologous comparison, pharmacological characterisation were carried out in rat brain synaptosomes by using [3H]-L-glutamate, showed that the whole PhTx4 fraction as well as the pure toxins PnTx4-3, Tx4(6-1) and Tx4(5-5) obtained of this fraction, were able to inhibit the glutamate uptake in the micromolar concentration range. PnTx4-3 inhibits the glutamate uptake in a dose dependent manner, with an IC50 of approximately 1 microM. PnTx4-3 is highly homologous to the Tx4(6-1) and Tx4(5-5) toxins previously described from the same fraction.
Authors:
Leida Calegário Oliveira; Maria Elena De Lima; Adriano M C Pimenta; Pascal Mansuelle; Hervé Rochat; Marta N Cordeiro; Michael Richardson; Suely G Figueiredo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  42     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2004-02-03     Completed Date:  2004-03-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  793-800     Citation Subset:  IM    
Affiliation:
Departamento de Fisiologia e Farmacologia, Instituto de Ciencias Biologicas, UFMG Av. Antônio Carlos, 6627-Pampulha Caixa Postal 486-31270-901, Belo Horizonte, MG, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Brain / drug effects,  metabolism
Diptera
Glutamic Acid / drug effects*,  metabolism
Male
Mice
Molecular Sequence Data
Neuropeptides / chemistry,  toxicity*
Neurotoxins / chemistry,  toxicity*
Rats
Rats, Wistar
Spider Venoms / chemistry,  toxicity*
Spiders*
Chemical
Reg. No./Substance:
0/Neuropeptides; 0/Neurotoxins; 0/PnTx4-3; 0/Spider Venoms; 56-86-0/Glutamic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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