SURAMIN ANALOGS, DIVALENT-CATIONS AND ATP-GAMMA-S AS INHIBITORS OF ECTO-ATPASE

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 classi fication of P-2 (nucleotide) receptors. We therefore studied suramin a nd several of its analogs, divalent cations and ATP gamma S for their ability to inhibit ecto-ATPase in human blood cells. Suramin itself an d Ni2+ were the more potent, non-competitive inhibitors with micromola r affinity. ATP gamma S also displayed micromolar affinity and inhibit ed ecto-ATPase competitively. The data obtained with the divalent cati ons demonstrate that coordination of the phosphate chain but not the N 7 of the adenine ring is required for the breakdown of ATP by ecto-ATP ase. Divalent cations that coordinate both the phosphate chain and N7 inhibit ecto-ATPase in a non-competitive manner.