title: The suramin analogue NF279 is a novel and potent antagonist selective for the P2X(1) receptor.
abstract: The suramin analogue 8,8'-(carbonylbis(imino-4, 1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)) bis(1,3,5-naphthalenetrisul fonic acid) (NF279) was analysed with respect to its potency and P2X receptor subtype selectivity. Two-electrode voltage-clamp measurements were performed with Xenopus laevis oocytes expressing homomultimeric rat P2X(1), P2X(2), P2X(3) and human P2X(4) receptors. For the fast desensitising P2X(1) and P2X(3) receptors, IC(50) values strongly depended on whether oocytes were pre-incubated with NF279 prior to ATP superfusion or exposed to NF279 simultaneously with ATP. With a 10 s pre-incubation period of NF279, IC(50) values of 19 nM and 1.62 microM were obtained for rat P2X(1) and P2X(3), respectively. Without pre-incubation, IC(50) values amounted to 2 microM and 85.5 microM for P2X(1) and P2X(3), respectively. For the non-desensitising rat P2X(2) receptor NF279 appeared to act as a competitive antagonist with an IC(50) value of 0.76 microM and a K(B) value of 0.36 microM, as derived from Schild analysis. P2X(4) receptors were the least sensitive subtypes for NF279 (IC(50)>300 microM). The antagonism was fully reversible at all P2X subtypes analysed. Our results indicate that NF279 is a potent P2X(1) receptor-selective and reversible antagonist.
authors.affiliation: Department of Pharmacology, Biocentre Niederursel, University of Frankfurt, Marie-Curie-Strasse 9, D-60439 Frankfurt/M, Germany. jrett@okay.net
authors.forename: J
authors.initials: J
authors.lastname: Rettinger
authors.forename: G
authors.initials: G
authors.lastname: Schmalzing
authors.forename: S
authors.initials: S
authors.lastname: Damer
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Nickel
authors.forename: G
authors.initials: G
authors.lastname: Lambrecht
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005260:Female; D006801:Humans; D058914:Purinergic Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: C114657:NF 279; C546407:P2RX3 protein, human; C548226:P2RX4 protein, human; C546410:P2rx3 protein, rat; C548228:P2rx4 protein, rat; D058914:Purinergic Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D013498:Suramin; D000255:Adenosine Triphosphate