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Ecto-nucleotidases are plasma membrane-bound enzymes that sequentially dephosphorylate extracellular nucleotides such as ATP. This breakdown of ATP and other nucleotides obscures the characterization and classification of P2 (nucleotide) receptors. We therefore studied suramin and several of its analogs, divalent cations and ATP gamma S for their ability to inhibit ecto-ATPase in human blood cells. Suramin itself and Ni2+ were the more potent, non-competitive inhibitors with micromolar affinity. ATP gamma S also displayed micromolar affinity and inhibited ecto-ATPase competitively. The data obtained with the divalent cations demonstrate that coordination of the phosphate chain but not the N7 of the adenine ring is required for the breakdown of ATP by ecto-ATPase. Divalent cations that coordinate both the phosphate chain and N7 inhibit ecto-ATPase in a non-competitive manner.

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1 The eects of NF023, the symmetrical 3'-urea of 8-(benzamido)naphthalene-1,3,5-trisulphonic acid), and its parent compound suramin were investigated on vasoconstrictor responses to a,b-methylene ATP in rabbit isolated saphenous artery and vasodilator responses to ATP in noradrenaline-precontracted rabbit isolated thoracic aorta. 2 In rabbit isolated saphenous artery, a,b-methylene ATP-induced vasoconstrictor responses via P2X-receptors were concentration-dependently and competitively antagonised by NF023 (30 ± 300 mM; pA 2 =5.69+0.04). Suramin (100 ± 1000 mM) also competitively blocked vasoconstrictor responses to a,bmethylene ATP, albeit with lower potency (pA 2 =4.79+0.05). In contrast, NF023 (100 mM) did not signi®cantly aect contractile responses to noradrenaline or histamine in the saphenous artery. 3 In noradrenaline-precontracted rabbit isolated thoracic aorta preparations, ATP (3 ± 3000 mM) concentration-dependently induced relaxations via endothelium-dependent or smooth muscle P2Y-receptor subtypes. NF023 (30 ± 300 mM) failed to block relaxant responses to ATP at endotheliumdependent P2Y-receptors, whereas suramin (100 ± 1000 mM) did antagonise endothelium-dependent vasodilator responses to ATP. Neither NF023 (100 mM) nor suramin (300 mM) in¯uenced vasorelaxant responses to ATP via endothelium-independent P2Y-receptors. 4 In conclusion, this study outlines the selectivity of NF023 as an eective P2X-receptor antagonist in rabbit isolated blood vessels without aecting endothelium-dependent or endothelium-independent P2Y-receptor subtypes, adrenoceptors or histamine receptors.