title: Polyamine spider toxins are potent un-competitive antagonists of rat cortex excitatory amino acid receptors.
abstract: 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 microM N-methyl-D-aspartate (NMDA) with 10 microM glycine were blocked by both of the polyamine toxins in a dose-dependent manner. Both compounds had similar potencies against 100 microM kainate or 50 microM (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (L-AMPA). Oscillatory responses to 2 microM 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.
authors.affiliation: Monsanto Corporate Research, Chesterfield, MO 63198.
authors.forename: M S
authors.initials: MS
authors.lastname: Davies
authors.forename: M P
authors.initials: MP
authors.lastname: Baganoff
authors.forename: E V
authors.initials: EV
authors.lastname: Grishin
authors.forename: T H
authors.initials: TH
authors.lastname: Lanthorn
authors.forename: T M
authors.initials: TM
authors.lastname: Volkova
authors.forename: G B
authors.initials: GB
authors.lastname: Watson
authors.forename: R C
authors.initials: RC
authors.lastname: Wiegand
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013111:Spider Venoms / Q000494:pharmacology*; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D007210:Indoleacetic Acids; D011073:Polyamines; D017981:Receptors, Neurotransmitter; D013111:Spider Venoms; C054141:argiotoxin 659; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid