Comparison of some arthropod toxins and toxin fragments as antagonists of excitatory amino acid-induced excitation of rat spinal neurones.
Wasp and spider venom toxins, which block glutamatergic transmission at invertebrate neuromuscular junctions, have recently been shown to block transmission at glutamate-operated synapses in mammalian central nervous system. Using the technique of iontophoresis on spinal neurones in anaesthetised rats, we have compared the action of five arthropod toxins and two toxin fragments, on responses to excitatory amino acids including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, kainate and N-methyl-D-aspartate (NMDA). All toxins caused greater than 70% mean reduction of non-NMDA responses. Only argiotoxin636 significantly reduced responses to NMDA. This blockade, like that induced by philanthotoxin-433 and -343, was readily reversible whereas blockade induced by Joro Spider toxin or Nephila Spider toxin was less readily reversible. Neither 2,4-dihydroxyphenylacetate nor 2,4-dihydroxyphenylacetylasparagine blocked NMDA or non-NMDA responses. It appears, therefore that small structural differences in the polyamine part of these toxin molecules give rise to different activity profiles with respect to selectivity and reversibility.
Jones
M G
MG
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Lodge
D
D
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001180:Arthropod Venoms / Q000494:pharmacology*; D001216:Asparagine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007210:Indoleacetic Acids; D007478:Iontophoresis; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D014862:Wasp Venoms / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D001180:Arthropod Venoms; D007210:Indoleacetic Acids; D009498:Neurotoxins; D010636:Phenols; D010648:Phenylacetates; D011073:Polyamines; D014862:Wasp Venoms; C558368:argiotoxin-636; C054470:2,4-dihydroxyphenylacetylasparagine; C074003:philanthotoxin 343; D007051:Ibotenic Acid; C054012:2,4-dihydroxyphenylacetic acid; D016202:N-Methylaspartate; D001216:Asparagine; C034092:delta-philanthotoxin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid