Description:
<jats:title>Abstract</jats:title><jats:p>Membrane currents and changes in the intracellular Ca<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) were measured in HEK293 cells transfected with the human P2X<jats:sub>3</jats:sub> receptor (HEK293‐hP2X<jats:sub>3</jats:sub>). RT‐PCR and immunocytochemistry indicated the additional presence of endogenous P2Y<jats:sub>1</jats:sub> and to some extent P2Y<jats:sub>4</jats:sub> receptors. P2 receptor agonists induced inward currents in HEK293‐hP2X<jats:sub>3</jats:sub> cells with the rank order of potency α,β‐meATP ≈ ATP > ADP‐β‐S > UTP. A comparable rise in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> was observed after the slow superfusion of ATP, ADP‐β‐S and UTP; α,β‐meATP was ineffective. These data, in conjunction with results obtained by using the P2 receptor antagonists TNP‐ATP, PPADS and MRS2179 indicate that the current response to α,β‐meATP is due to P2X<jats:sub>3</jats:sub> receptor activation, while the ATP‐induced rise in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> is evoked by P2Y<jats:sub>1</jats:sub> and P2Y<jats:sub>4</jats:sub> receptor activation. TCE depressed the α,β‐meATP current in a manner compatible with a non‐competitive antagonism. The ATP‐induced increase of [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> was much less sensitive to the inhibitory effect of TCE than the current response to α,β‐meATP. The present study indicates that in HEK293‐hP2X<jats:sub>3</jats:sub> cells, TCE, but not ethanol, potently inhibits ligand‐gated P2X<jats:sub>3</jats:sub> receptors and, in addition, moderately interferes with G protein‐coupled P2Y<jats:sub>1</jats:sub> and P2Y<jats:sub>4</jats:sub> receptors. Such an effect may be relevant for the interruption of pain transmission in dorsal root ganglion neurons following ingestion of chloral hydrate or trichloroethylene.</jats:p>