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

Florentina Soto; Günter Lambrecht; Peter Nickel; Walter Stühmer; Andreas E. Busch

doi:10.1016/S0028-3908(98)00158-0

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

Florentina Soto, Günter Lambrecht, Peter Nickel, Walter Stühmer, Andreas E. Busch

Department of Ophthalmology and Visual Sciences

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

The suramin analogue 8, 8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive fashion P2X receptor-mediated responses in certain vascular and visceral smooth muscles. In the present study, the effect of NF023 on voltage-clamped Xenopus oocytes heterologously expressing homomultimeric P2X₁-P2X₄ as well as heteromultimeric P2X₂/P2X₃ receptors has been characterized. P2X₁ receptors were most sensitive to inhibition by NF023 with IC₅₀ values of 0.24 and 0.21 μM for the rat and human homologue, respectively. P2X₃ receptors have an intermediate sensitivity with IC₅₀ values of 8.5 and 28.9 μM for rat and human subtypes, respectively and P2X₂ was the least sensitive subtype (IC₅₀ > 50 μM). P2X₄ receptors were insensitive to NF023 at concentrations up to 100 μM. Coexpression of rat P2X₃ with rat P2X₃ resulted in receptors whose sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X₃ receptors (αβmeATP as agonist; IC₅₀ = 1.4 and 1.6 μM, respectively). NF023 inhibited P2X₁ receptors in a voltage-insensitive manner. In addition, NF023 (5 and 30 μM) caused a shift of the concentration-response curve to the right without affecting the maximal response to ATP (K(B) = 1.1 ± 0.2 μM). Our results indicate that NF023 is a subtype-selective and surmountable antagonist at P2X₁ receptors heterologously expressed in Xenopus oocytes.

Original language	English
Pages (from-to)	141-149
Number of pages	9
Journal	Neuropharmacology
Volume	38
Issue number	1
DOIs	https://doi.org/10.1016/S0028-3908(98)00158-0
State	Published - Jan 1999

Keywords

ATP
Competitive antagonism
NF023
P2X receptor
Suramin analogue

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10.1016/S0028-3908(98)00158-0

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@article{7a8367bd7fd34ed6a258cbd033e58abc,

title = "Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors",

abstract = "The suramin analogue 8, 8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive fashion P2X receptor-mediated responses in certain vascular and visceral smooth muscles. In the present study, the effect of NF023 on voltage-clamped Xenopus oocytes heterologously expressing homomultimeric P2X1-P2X4 as well as heteromultimeric P2X2/P2X3 receptors has been characterized. P2X1 receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and 0.21 μM for the rat and human homologue, respectively. P2X3 receptors have an intermediate sensitivity with IC50 values of 8.5 and 28.9 μM for rat and human subtypes, respectively and P2X2 was the least sensitive subtype (IC50 > 50 μM). P2X4 receptors were insensitive to NF023 at concentrations up to 100 μM. Coexpression of rat P2X3 with rat P2X3 resulted in receptors whose sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X3 receptors (αβmeATP as agonist; IC50 = 1.4 and 1.6 μM, respectively). NF023 inhibited P2X1 receptors in a voltage-insensitive manner. In addition, NF023 (5 and 30 μM) caused a shift of the concentration-response curve to the right without affecting the maximal response to ATP (K(B) = 1.1 ± 0.2 μM). Our results indicate that NF023 is a subtype-selective and surmountable antagonist at P2X1 receptors heterologously expressed in Xenopus oocytes.",

keywords = "ATP, Competitive antagonism, NF023, P2X receptor, Suramin analogue",

author = "Florentina Soto and G{\"u}nter Lambrecht and Peter Nickel and Walter St{\"u}hmer and Busch, {Andreas E.}",

note = "Funding Information: We thank Dr A. Blake and D. Julius for providing the rat P2X 2 cDNA, Dr Gary Buell and Alan North for supplying the rat P2X 1 and P2X 3 cDNA and Dr Gillian Busch for critically reading the manuscript. We are indebted to Katja Antonnen for the cRNA synthesis and Susanne Voigt for the preparation and injection of Xenopus laevis oocytes. G.L. and W.S. gratefully acknowledge the financial support of the Fonds der Chemischen Industrie (Germany). Supported by a grant of the Deutsche Forchungsgemeinschaft (La 350/7-1) to G.L.",

year = "1999",

month = jan,

doi = "10.1016/S0028-3908(98)00158-0",

language = "English",

volume = "38",

pages = "141--149",

journal = "Neuropharmacology",

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T1 - Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors

AU - Soto, Florentina

AU - Lambrecht, Günter

AU - Nickel, Peter

AU - Stühmer, Walter

AU - Busch, Andreas E.

N1 - Funding Information: We thank Dr A. Blake and D. Julius for providing the rat P2X 2 cDNA, Dr Gary Buell and Alan North for supplying the rat P2X 1 and P2X 3 cDNA and Dr Gillian Busch for critically reading the manuscript. We are indebted to Katja Antonnen for the cRNA synthesis and Susanne Voigt for the preparation and injection of Xenopus laevis oocytes. G.L. and W.S. gratefully acknowledge the financial support of the Fonds der Chemischen Industrie (Germany). Supported by a grant of the Deutsche Forchungsgemeinschaft (La 350/7-1) to G.L.

PY - 1999/1

Y1 - 1999/1

N2 - The suramin analogue 8, 8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive fashion P2X receptor-mediated responses in certain vascular and visceral smooth muscles. In the present study, the effect of NF023 on voltage-clamped Xenopus oocytes heterologously expressing homomultimeric P2X1-P2X4 as well as heteromultimeric P2X2/P2X3 receptors has been characterized. P2X1 receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and 0.21 μM for the rat and human homologue, respectively. P2X3 receptors have an intermediate sensitivity with IC50 values of 8.5 and 28.9 μM for rat and human subtypes, respectively and P2X2 was the least sensitive subtype (IC50 > 50 μM). P2X4 receptors were insensitive to NF023 at concentrations up to 100 μM. Coexpression of rat P2X3 with rat P2X3 resulted in receptors whose sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X3 receptors (αβmeATP as agonist; IC50 = 1.4 and 1.6 μM, respectively). NF023 inhibited P2X1 receptors in a voltage-insensitive manner. In addition, NF023 (5 and 30 μM) caused a shift of the concentration-response curve to the right without affecting the maximal response to ATP (K(B) = 1.1 ± 0.2 μM). Our results indicate that NF023 is a subtype-selective and surmountable antagonist at P2X1 receptors heterologously expressed in Xenopus oocytes.

AB - The suramin analogue 8, 8'-(carbonylbis(imino-3,1-phenylene carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a competitive fashion P2X receptor-mediated responses in certain vascular and visceral smooth muscles. In the present study, the effect of NF023 on voltage-clamped Xenopus oocytes heterologously expressing homomultimeric P2X1-P2X4 as well as heteromultimeric P2X2/P2X3 receptors has been characterized. P2X1 receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and 0.21 μM for the rat and human homologue, respectively. P2X3 receptors have an intermediate sensitivity with IC50 values of 8.5 and 28.9 μM for rat and human subtypes, respectively and P2X2 was the least sensitive subtype (IC50 > 50 μM). P2X4 receptors were insensitive to NF023 at concentrations up to 100 μM. Coexpression of rat P2X3 with rat P2X3 resulted in receptors whose sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X3 receptors (αβmeATP as agonist; IC50 = 1.4 and 1.6 μM, respectively). NF023 inhibited P2X1 receptors in a voltage-insensitive manner. In addition, NF023 (5 and 30 μM) caused a shift of the concentration-response curve to the right without affecting the maximal response to ATP (K(B) = 1.1 ± 0.2 μM). Our results indicate that NF023 is a subtype-selective and surmountable antagonist at P2X1 receptors heterologously expressed in Xenopus oocytes.

KW - ATP

KW - Competitive antagonism

KW - NF023

KW - P2X receptor

KW - Suramin analogue

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U2 - 10.1016/S0028-3908(98)00158-0

DO - 10.1016/S0028-3908(98)00158-0

M3 - Article

C2 - 10193905

AN - SCOPUS:0033004707

SN - 0028-3908

VL - 38

SP - 141

EP - 149

JO - Neuropharmacology

JF - Neuropharmacology

IS - 1

ER -

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

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Keywords

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