Philanthotoxin blocks quisqualate‐, AMPA‐ and kainate‐, but not NMDA‐, induced excitation of rat brainstem neurones in vivo

Abstract

1 The effect of electrophoretic ejection of philanthotoxin (the polyamine toxin, from the Egyptian digger wasp) was tested on responses of brainstem and spinal neurones in the pentobarbitone-anaesthetized rat to excitatory amino acids. 2 Philanthotoxin caused a dose-dependent reduction of responses to quisqualate, a-amino-3-hydroxy-5-phenyl-4-isoxazolepropionate (AMPA) and kainate with little effect on those to N-methyl-D-aspartate (NMDA). 3 The time-course of this antagonist action was slow. In particular the rate of recovery was dependent on frequency of ejection of the agonist. This agonist-dependent recovery suggests that philanthotoxin has a channel blocking mode of action on mammalian central neurones.

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

“…99 In contrast, several polyaminecontaining toxins including ArgTX-636 (18), JSTX-3 (19), PhTX-433 (20), PhTX-343 (21), and NSTX-3 potently and selectively antagonized responses to non-NMDAR antagonists (including AMPA and KA) in rat spinal neurons 211 and rat brainstem neurons. 212 Two reports 213,214 portrayed aagatoxins as NMDAR-selective antagonists, but these toxins were later shown to potently antagonize recombinant GluR2-lacking AMPAR. 171,176 Clearly the confusion can be explained in terms of our current knowledge of receptor subunits and their relative distributions throughout the CNS.…”

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

“…A large number of naturally occurring AMPA and kainate receptor channel blockers, as well as a host of synthetic analogs, have been identified (Table 14), including argiotoxin-636 (Herlitze et al, 1993), Joro spider toxin (Blaschke et al, 1993), Ageltoxin-489 ( Washburn and Dingledine, 1996), philanthotoxin-433 (Jones et al, 1990), IEM-1460 (Magazanik et al, 1997), and N 1 -naphthylacetylspermine (Koike et al, 1997), which also blocks mutant Lurcher GluD2 channels. Some of these compounds have nonspecific actions at other ion channels (Welch et al, 2008).…”

Contrasting Actions of Philanthotoxin-343 and Philanthotoxin-(12) on Human Muscle Nicotinic Acetylcholine Receptors

“…1), a structurally close analog of PhTX-433, is one of many synthetic analogs of the natural product Bruce et al, 1990;Benson et al, 1992Benson et al, , 1993Strømgaard et al, 1999Strømgaard et al, , 2000Bixel et al, 2000). It is a potent antagonist of ionotropic glutamate receptors mediating neuromuscular transmission in insects (Eldefrawi et al, 1988;Bruce et al, 1990), of ionotropic glutamate receptors of rat brain (Ragsdale et al, 1989;Jones et al, 1990;Brackley et al, 1993), and of recombinant, ionotropic glutamate receptors from rat (Brackley et al, 1993;Bä hring and Mayer, 1998). The interactions of PhTX-433 and PhTX-343 with vertebrate muscle-type nAChR have been studied electrophysiologically using frog muscle (Rozental et al, 1989) and the mouse BC 3 H1 cell line (Jayaraman et al, 1999) and with neuronal-type nAChR using insect cockroach thoracic ganglia (Rozental et al, 1989) and PC-12 cells .…”