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• W2113466780 abstract "The whole-cell patch-clamp technique was used to record current responses to nucleotides and nucleosides in human embryonic kidney HEK293 cells transfected with the human purinergic P2X 3 receptor. When guanosine 5′- O -(3-thiodiphosphate) was included into the pipette solution, UTP at concentrations that did not alter the holding current facilitated the α,β-methylene ATP (α,β-meATP)-induced current. ATP and GTP, but not UDP or uridine, had an effect similar to that of UTP. Compounds known to activate protein kinase C (PKC) acted like the nucleoside triphosphates investigated, whereas various PKC inhibitors invariably reduced the effects of both PKC activators and UTP. The substitution by Ala of Ser/Thr residues situated within PKC consensus sites of the P2X 3 receptor ectodomain either abolished (PKC2 and PKC3; T134A, S178A) or did not alter (PKC4 and PKC6; T196A, S269A) the UTP-induced potentiation of the α,β-meATP current. Both the blockade of ecto-protein kinase C activity and the substitution of Thr-134 or Ser-178 by Ala depressed the maximum of the concentration-response curve for α,β-meATP without altering the EC 50 values. Molecular simulation of the P2X 3 receptor structure indicated no overlap between assumed nucleotide binding domains and the relevant phosphorylation sites PKC2 and PKC3. α,β-meATP-induced currents through native homomeric P2X 3 receptors of rat dorsal root ganglia were also facilitated by UTP. In conclusion, it is suggested that low concentrations of endogenous nucleotides in the extracellular space may prime the sensitivity of P2X 3 receptors toward the effect of subsequently applied (released) higher agonistic concentrations. The priming effect of nucleotides might be attributable to a phosphorylation of PKC sites at the ectodomain of P2X 3 receptors." @default.
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• W2113466780 date "2005-08-24" @default.
• W2113466780 modified "2023-10-11" @default.
• W2113466780 title "Regulation of Human Recombinant P2X₃Receptors by Ecto-Protein Kinase C" @default.
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• W2113466780 doi "https://doi.org/10.1523/jneurosci.2028-05.2005" @default.
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