POLYAMINE SPIDER TOXINS ARE POTENT UN-COMPETITIVE ANTAGONISTS OF RAT CORTEX EXCITATORY AMINO-ACID RECEPTORS

We examined the effect of argiopine and argiopinine 3, low molecular weight polyamine venom components of the spider Argiope lobata, on rat cortical excitatory amino acid (EAA) receptors expressed in Xenopus oocytes. Responses to 100-mu-M N-methyl-D-aspartate (NMDA) with 10-mu-M glycine were blocked by both of the polyamine toxins in a dose-dependent manner. Both compounds had similar potencies against 100-mu-M kainate or 50-mu-M (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (L-AMPA). Oscillatory responses to 2-mu-M quisqualate were unaffected by either polyamine toxin. Increasing concentrations of either NMDA, kainate or AMPA were unable to overcome the antagonism by either spider toxin. We were able to demonstrate a use-dependent phenomenon similar to that of phencyclidine; neither polyamine toxin affected the NMDA, kainate or AMPA response without the presence of the respective agonist.