The effect of spider toxin PhTx3-4, ω-conotoxins MVIIA and MVIIC on glutamate uptake and on capsaicin-induced glutamate release and [Ca2+]i in spinal cord synaptosomes.
In spinal cord synaptosomes, the spider toxin PhTx3-4 inhibited capsaicin-stimulated release of glutamate in both calcium-dependent and -independent manners. In contrast, the conus toxins, ω-conotoxin MVIIA and xconotoxin MVIIC, only inhibited calcium-dependent glutamate release. PhTx3-4, but not ω-conotoxin MVIIA or xconotoxin MVIIC, is able to inhibit the uptake of glutamate by synaptosomes, and this inhibition in turn leads to a decrease in the Ca(2+)-independent release of glutamate. No other polypeptide toxin so far described has this effect. PhTx3-4 and ω-conotoxins MVIIC and MVIIA are blockers of voltage-dependent calcium channels, and they significantly inhibited the capsaicin-induced rise of intracellular calcium [Ca(2+)](i) in spinal cord synaptosomes, which likely reflects calcium entry through voltage-gated calcium channels. The inhibition of the calcium-independent glutamate release by PhTx3-4 suggests a potential use of the toxin to block abnormal glutamate release in pathological conditions such as pain.
Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Jomara M
JM
Gonçaves
Juliano
J
Ferreira
Marco Antonio M
MA
Prado
Marta N
MN
Cordeiro
Michael
M
Richardson
Ana Cristina do Nascimento
AC
Pinheiro
Marco A Romano
MA
Silva
Celio José de Castro
CJ
Junior
Alessandra H
AH
Souza
Marcus Vinicius
MV
Gomez
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D005453:Fluorescence; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000633:toxicity; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020960:omega-Conotoxins / Q000633:toxicity*
D009479:Neuropeptides; D013111:Spider Venoms; C098736:Tx3 neurotoxin; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D018698:Glutamic Acid; C078452:ziconotide; D002211:Capsaicin; D002118:Calcium