RT Journal Article
SR Electronic
T1 Selective antagonism of native and cloned kainate and NMDA receptors by polyamine-containing toxins.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1573
OP 1580
VO 266
IS 3
A1 P T Brackley
A1 D R Bell
A1 S K Choi
A1 K Nakanishi
A1 P N Usherwood
YR 1993
UL http://jpet.aspetjournals.org/content/266/3/1573.abstract
AB Antagonism of rat excitatory amino acid receptors by a synthetic analog [philanthotoxin-343 (PhTX-343)] of a polyamine amide, wasp toxin (philanthotoxin-433) and a structurally related spider toxin, argiotoxin-636 (ArgTX-636), was examined in Xenopus oocytes injected with rat brain RNA or RNA transcribed from the excitatory amino acid receptor clones GluR1, GluR2 and NMDAR1. Antagonism of both kainate- and N-methyl-D-aspartate (NMDA)-elicited responses by PhTX-343 and ArgTX-636 was reversible, noncompetitive and partly voltage-dependent. Dose-inhibition curves were constructed using EC50 concentrations of kainate (100 microM) and N-methyl-D-aspartate (33 microM) in the presence of variable concentrations of ArgTX-636 and PhTX-343. In oocytes injected with rat brain RNA, IC50s for antagonism of kainate-induced currents were similar, i.e., 0.07 microM and 0.12 microM for ArgTX-636 and PhTX-343, respectively, whereas IC50s for antagonism of NMDA-induced currents were dissimilar, i.e., 0.04 microM for ArgTX-636 and 2.5 microM for PhTX-343. In oocytes expressing NMDAR1, IC50s were similar to those for the antagonism of NMDA-induced currents of oocytes injected with rat brain RNA. PhTX-343 and ArgTX-636 were more or less equally potent (IC50s were 2.8 microM and 3.4 microM, respectively) antagonists of the response of GluR1 to 100 microM kainate. However, GluR1 was approximately 50 times less sensitive to the toxins than non-N-methyl-D-aspartate receptors expressed in oocytes injected with rat brain RNA. Receptors co-expressed from GluR1 + GluR2 were virtually insensitive to PhTX-343 (IC50 = 270 microM) and to ArgTX-343 (IC50 approximately 300 microM).