Arylamine spider toxins antagonize NMDA receptor-mediated synaptic transmission in rat hippocampal slices.
The effects of arylamine spider toxins on synaptic transmission in rat hippocampal slices were investigated. Two different responses were monitored: the AMPA receptor-mediated population spike recorded in control buffer (selectively antagonized by DNQX) and the NMDA receptor-mediated EPSP recorded in nominally magnesium-free buffer containing 20 microM DNQX (selectively antagonized by AP5, AP7, and dizocilpine (MK-801)). The synthetic arylamine spider toxins JSTX-3, argiotoxin-636, and argiotoxin-659 were 26 to 73 times more potent at antagonizing the NMDA receptor-mediated EPSP (IC50 values ranging from 12 to 24 microM) than the AMPA receptor-mediated population spike (IC50 values ranging from 612 to 878 microM). These results indicate that arylamine spider toxins are selective antagonists of NMDA receptors in the mammalian CNS.
Mueller
A L
AL
Natural Product Sciences, Inc., Salt Lake City, Utah 84108.
Albensi
B C
BC
Ganong
A H
AH
Reynolds
L S
LS
Jackson
H
H
D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013111:Spider Venoms / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D007210:Indoleacetic Acids; C044936:JSTX spider toxin; D009498:Neurotoxins; D010648:Phenylacetates; D011073:Polyamines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D013111:Spider Venoms; C558368:argiotoxin-636; C054141:argiotoxin 659