2',3'-O-(2,4,6-TRINITROPHENYL)ADENOSINE 5'-TRIPHOSPHATE (TNP-ATP) - ANANOMOLAR AFFINITY ANTAGONIST AT RAT MESENTERIC-ARTERY P2X RECEPTOR-ION CHANNELS

1 P2X receptor activation by alpha,beta-meATP evoked inward currents i n acutely dissociated rat mesenteric artery smooth muscle cells and co ntractions of whole artery rings. 2 The selective P2X(1) and P2X(3) re ceptor antagonist TNP-ATP inhibited P2X receptor mediated inward curre nts in response to 3 mu M alpha,beta-meATP (an similar to EC90 concent ration) with an IC50 of similar to 2 nM. This provides further evidenc e 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 contra ctions with an IC50 of similar to 30 mu M and had non-specific effects on smooth muscle contraction. 4 The reduced potency of TNP-ATP in who le tissue experiments probably reflects the breakdown of TNP-ATP by nu cleotidases. Thus, TNP-ATP is of limited use in whole tissue experimen ts as a P2X receptor antagonist.