2′,3′-O-(2,4,6-trinitrophenyl)adenosine 5′-triphosphate (TNP-ATP) -: a nanomolar affinity antagonist at rat mesenteric artery P2X receptor ion channels

1 P2X receptor activation by alpha,beta-meATP evoked inward currents in acutely dissociated rat mesenteric artery smooth muscle cells and contractions of whole artery rings. 2 The selective P2X(1) and P2X(3) receptor antagonist TNP-ATP inhibited P2X receptor mediated inward currents in response to 3 mu M alpha,beta-meATP (an similar to EC(90) concentration) with an IC(50) of similar to 2 nM. This provides further evidence that the P2X receptor underlying membrane depolarisation associated with P2X receptor activation can be accounted for by the expression of P2X(1) receptors. 3 TNP-ATP inhibited alpha,beta-meATP induced contractions with an IC(50) of similar to 30 mu M and had non-specific effects on smooth muscle contraction. 4 The reduced potency of TNP-ATP in whole tissue experiments probably reflects the breakdown of TNP-ATP by nucleotidases. Thus, TNP-ATP is of limited use in whole tissue experiments as a P2X receptor antagonist.