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• W2040184460 abstract "Rapid desensitization of ligand‐gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast‐channel activation difficult. Investigation of the antagonist pharmacology of ATP‐sensitive homomeric P2X 3 receptors is limited by agonist‐evoked fast‐desensitization kinetics. In the present studies, chimeric receptors were created using the coding sequence for the N‐terminus and the first transmembrane domain of either the nondesensitizing human P2X 2a or fast‐desensitizing P2X 3 receptor joined to the sequence encoding the extracellular loop, second transmembrane domain, and C‐terminus of the other receptor (designated P2X 2–3 and P2X 3–2 , respectively). These clones were stably transfected into 1321N1 astrocytoma cells for biophysical and pharmacological experiments using both electrophysiological and calcium‐imaging methods. Chimeric P2X 2–3 and P2X 3–2 receptors were inwardly rectifying and agonist responses showed desensitization properties similar to the wild‐type human P2X 2a and P2X 3 receptors, respectively. The P2X 2–3 chimera displayed an agonist pharmacological profile similar to the P2X 3 wild‐type receptor being activated by low concentrations of both ATP and α , β ‐meATP. In contrast, the P2X 3–2 chimera had markedly reduced sensitivity to both agonists. The P2X 3 receptor antagonists TNP‐ATP and A‐317491 were shown to be potent, competitive antagonists of the P2X 2–3 chimera ( K i =2.2 and 52.1 n M , respectively), supporting the hypothesis that rapid receptor desensitization can mask the competitive antagonism of wild‐type homomeric P2X 3 receptors. British Journal of Pharmacology (2003) 140 , 202–210. doi: 10.1038/sj.bjp.0705411" @default.
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• W2040184460 date "2003-09-01" @default.
• W2040184460 modified "2023-10-14" @default.
• W2040184460 title "2′, 3′-<i>O</i> -(2,4,6,Trinitrophenyl)-ATP and A-317491 are competitive antagonists at a slowly desensitizing chimeric human P2X₃ receptor" @default.
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• W2040184460 doi "https://doi.org/10.1038/sj.bjp.0705411" @default.
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