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- W127096679 abstract "P2X3 receptors are ligand gated ion channels activated by ATP. In the periphery, these receptors are located on nociceptive neurons which convey inflammatory pain information to the central nervous system. Thus, these receptors are likely targets for analgesic drug development. Here, we devise an electrophysiological method to determine the mechanism of action (competitive or non-competitive inhibition) by which compounds exert their antagonistic effects on a P2X2-3 chimeric receptor. By applying a fixed concentration of the antagonist in the presence of the P2X3 receptor agonist alpha, beta-methylene ATP, we can compare the rate of inhibition at different concentrations of the agonist. We show that the rate of inhibition of the P2X3 antagonist TNP-ATP is linearly dependent on the concentration of agonist with which it is co-applied, consistent with the pharmacological profile of TNP-ATP acting as a competitive antagonist at the receptor's ligand binding site. However, the rate of inhibition of Compound A is independent of the agonist concentration in which it is co-applied, suggesting that the site of inhibition is not competitive with that of the agonist. These results are consistent with radioligand binding data of Compound A on a homomeric P2X3 receptor. These data therefore provide an electrophysiological kinetic determination of the competitivity of a compound at a ligand gated ion channel." @default.
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- W127096679 date "2008-04-01" @default.
- W127096679 modified "2023-10-18" @default.
- W127096679 title "Electrophysiological determination of antagonist mechanism of action at a P2X2‐3 chimeric receptor" @default.
- W127096679 doi "https://doi.org/10.1096/fasebj.22.2_supplement.626" @default.
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