Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer.
Glutamate concentration increases significantly in the extracellular compartment during brain ischaemia and anoxia. This increase has an important Ca(2+)-independent component, which is due in part to the reversal of glutamate transporters of the plasma membrane of neurons and glia. The toxin phoneutriatoxin 3-4 (Tx3-4) from the spider Phoneutria nigriventer has been reported to decrease the evoked glutamate release from synaptosomes by inhibiting Ca(2+) entry via voltage-dependent Ca(2+) channels. However, we report here that Tx3-4 is also able to inhibit the uptake of glutamate by synaptosomes in a time-dependent manner and that 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. Our results suggest that Tx3-4 can be a valuable tool in the investigation of function and dysfunction of glutamatergic neurotransmission in diseases such as ischaemia.
Reis
H J
HJ
Divisão de Biologia Celular, Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brasil.
Prado
M A
MA
Kalapothakis
E
E
Cordeiro
M N
MN
Diniz
C R
CR
De Marco
L A
LA
Gomez
M V
MV
Romano-Silva
M A
MA
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D009479:Neuropeptides / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013112:Spiders; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020960:omega-Conotoxins
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002121:Calcium Channel Blockers; D009479:Neuropeptides; D009498:Neurotoxins; D010455:Peptides; C098736:Tx3 neurotoxin; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D018698:Glutamic Acid; D004533:Egtazic Acid; D011189:Potassium Chloride; D014701:Veratridine; D002118:Calcium