Antagonism by the suramin analogue NF279 on human P2X(1) and P2X(7) receptors

The effect of the suramin analogue 8,8'-(carbonylbis(imino-4,1-phenylenecar bonylimino-4,1-phenylenecarbonylimino))bis(1,3,5-naphthalenetrisulfonic aci d) (NF279) was analyzed on human P2X(1) and P2X(7) receptor subtypes (human P2X(1) and human P2X(7)) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. At activating ATP concentr ations of 1 mu M (human P2X(1)) and 10 mu M ATP (human P2X(7)), IC50 values of 0.05 mu M and 2.8 mu M were found for human P2X(1) and human P2X(7) rec eptors, respectively. An increase in the activating [ATP] shifted the NF279 concentration-inhibition curve rightwards for both receptors. NF279 slowed the activation of both human P2X(1) and human P2X(7) as well as the desens itization of human P2X(1). The data support a model in which desensitizatio n of P2X(1), is dependent on preceding activation of these P2X receptors. I t is concluded that NF279 acts as a competitive antagonist with much higher potency at human P2X(1) than at P2X(7) receptors. NF279 may hence be suite d to discriminate between both receptors in native tissues. (C) 2000 Elsevi er Science B.V. All rights reserved.