Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer

Biochem J. 1999 Oct 15;343 Pt 2(Pt 2):413-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Transport System X-AG
  • Animals
  • Binding, Competitive
  • Biological Transport / drug effects
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / pharmacology
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • Neuropeptides / pharmacology*
  • Neurotoxins / pharmacology*
  • Peptides / pharmacology*
  • Potassium Chloride / antagonists & inhibitors
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Wistar
  • Spiders*
  • Synaptosomes / drug effects*
  • Synaptosomes / metabolism
  • Veratridine / antagonists & inhibitors
  • Veratridine / pharmacology
  • omega-Conotoxins*

Substances

  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Calcium Channel Blockers
  • Neuropeptides
  • Neurotoxins
  • Peptides
  • Tx3 neurotoxin
  • omega-Conotoxins
  • omega-conotoxin-MVIIC
  • Glutamic Acid
  • Egtazic Acid
  • Potassium Chloride
  • Veratridine
  • Calcium