Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors

The suramin analogue 8,8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bi s(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive f ashion P2X receptor-mediated responses in certain vascular and visceral smo oth muscles. In the present study, the effect of NF023 on voltage-clamped X enopus oocytes heterologously expressing homomultimeric P2X(1)-P2X(4) as we ll as heteromultimeric P2X(2)/P2X(3) receptors has been characterized. P2X( 1) receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and 0.21 mu M for the rat and human homologue, respectively. P2X(3) r eceptors have an intermediate sensitivity with IC50 values of 8.5 and 28.9 mu M for rat and human subtypes, respectively and P2X(2) was the least sens itive subtype (IC50 > 50 mu M). P2X(4) receptors were insensitive to NF023 at concentrations up to 100 mu M. Coexpression of rat P2X(3) with rat P2X(2 ) resulted in receptors whose sensitivity to NF023 was identical to that ob tained for homomultimeric rat P2X, receptors; (alpha beta meATP as agonist; IC50 = 1.4 and 1.6 mu M, respectively), NF023 inhibited P2X(1) receptors i n a voltage-insensitive manner. In addition, NF023 (5 and 30 mu M) caused a shift of the concentration-response curve to the right without affecting t he maximal response to ATP (K-B = 1.1 +/- 0.2 mu M). Our results indicate t hat NF023 is a subtype-selective and surmountable antagonist at P2X(1) rece ptors heterologously expressed in Xenopus oocytes. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.