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

Abstract

1. P2X receptor activation by α,β-meATP evoked inward currents in acutely dissociated rat mesenteric artery smooth muscle cells and contractions of whole artery rings. 2. The selective P2X1 and P2X3 receptor antagonist TNP-ATP inhibited P2X receptor mediated inward currents in response to 3 μM α,β-meATP (an ~ EC90 concentration) with an IC50 of ~ 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 P2X1 receptors. 3. TNP-ATP inhibited α,β-meATP induced contractions with an IC50, of ~ 30 μM 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.