Molecular characterization and pharmacological properties of the human P2X₃ purinoceptor

Using PCR and library screening techniques, a cDNA encoding an ATP ligand-gated channel has been isolated from human heart. The full-length cDNA encodes a protein 397 amino acids long which shows a high amino-acid sequence identity with the rat P2X₃ purinoceptor (93%). By fluorescence in situ hybridization, the human P2X₃ gene has been mapped to region q12 of chromosome 11. Tissue distribution analysis of human P2X₃ receptor mRNA shows a restricted expression pattern, i.e. transcripts are limited to the spinal cord and heart. This result contrasts with the distribution of the rat P2X₃ receptor which was detected exclusively in sensory neurons of trigeminal, dorsal root and nodose ganglia. Heterologous expression of human P2X₃ cRNA in Xenopus oocytes generates a fast desensitizing ATP-activated channel with pharmacological properties resembling the profile of the rat homologue receptor. Thus, the order of agonist potency is 2MeSATP > ATP > αβ-meATP > CTP > βα-meATP ≃ ADP. Moreover, ATP-evoked currents on human P2X₃ receptor are efficiently blocked in a reversible manner by the purinoceptor antagonists, suramin and PPADS.