The suramin analogue NF279 is a novel and potent antagonist selective for the P2X(1) receptor

The suramin analogue 8,8'-(carbonylbis(imino-4,1-phenylenecarbsnylimino-4,1 -phenylenecarbonylimino))bis(1,3,5-naphthalenetrisulfonic acid) (NF279) was analysed with respect to its potency and P2X receptor subtype selectivity. Two-electrode voltage-clamp measurements were performed with Xenopus laevi s oocytes expressing homomultimeric rat P2X(1), P2X(2), P2X(3) and human P2 X, receptors. For the fast desensitising P2X, and P2X(4) receptors, IC50 va lues strongly depended on whether oocytes were preincubated with NF279 prio r to ATP superfusion or exposed to NF279 simultaneously with ATP. With a 10 s pre-incubation period of NF279, IC50 values of 19 nM and 1.62 mu M were obtained for rat P2X(1) and P2X(3), respectively. Without pre-incubation, I C50 values amounted to 2 mu M and 85.5 mu M for P2X(1) and P2X(3), respecti vely. For the non-desensitising rat P2X(2) receptor NF279 appeared to act a s a competitive antagonist with an IC50 value of 0.76 mu M and a K-B value of 0.36 mu M, as derived from Schild analysis. P2X(4) receptors were the le ast sensitive subtypes for NF279 (IC50 > 300 mu M). The antagonism was full y reversible at all P2X subtypes analysed. Our results indicate that NF279 is a potent P2X(1) receptor-selective and reversible antagonist. (C) 2000 E lsevier Science Ltd. All rights reserved.