Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist, suramin

Balcar, Vladimír J.; Dias, Leonora S.; Li, Yang; Bennett, Maxwell R.

doi:10.1097/00001756-199512000-00016

Cited by 9 publications

(7 citation statements)

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“…The increase by suramin in the EC 50 of NMDA observed in the present study agrees with the findings of Balcar et al , (1995), who showed that suramin displaced binding of the competitive NMDA antagonist [ 3 H]‐CGP 39653 in slices of neocortex and hippocampus. In contrast, the observations of the present study do not appear to agree with those obtained by Nakazawa et al , (1995), who observed that suramin produced similar inhibition of current activated by 100 or 500 μM NMDA.…”

Section: Discussionsupporting

confidence: 93%

“…The IC 50 values for reactive blue 2 and suramin inhibition of NMDA-activated current obtained in the present study were 11 and 63 mM, respectively. These IC 50 values are consistent with results obtained by other investigators for displacement by suramin of speci®c binding of [ 3 H]-CGP 39653 in slices of neocortex and hippocampus (Balcar et al, 1995), suramin inhibition of NMDA-evoked ®ring of locus coeruleus neurones (FroÈ hlich et al, 1996), and inhibition by suramin and reactive blue 2 of NMDA-activated current in rat hippocampal neurones (Nakazawa et al, 1995). The potencies of suramin and reactive blue 2 for inhibition of P2X receptors vary depending upon the experimental preparation used, but are generally in the range 5 ± 180 mM for suramin (Nakazawa et al, 1991;Khakh et al, 1995;Garcia-Guzman et al, 1997) and 1 ± 40 mM for reactive blue 2 (Nakazawa et al, 1991;Fieber & Adams, 1991;Garcia-Guzman et al, 1997).…”

supporting

confidence: 91%

“…Like NMDA receptor‐channels, at least some types of P2X purinoceptors are inhibited by ethanol (Li et al , 1993a). Interestingly, results of recent studies have shown that the P2 purinoceptor antagonists suramin and reactive blue 2 inhibit radioligand binding to the NMDA receptor (Balcar et al , 1995), and NMDA‐activated current in CNS neurones (Nakazawa et al , 1995; Motin & Bennett, 1995). However, the mechanisms of action of each of these agents on the NMDA receptor have not been determined.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Peoples

1998

British J Pharmacology

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1 The action of suramin and reactive blue 2 on N-methyl-D-aspartate (NMDA)-activated ion current was studied in mouse hippocampal neurones in culture by use of whole-cell patch-clamp recording. 2 Suramin and reactive blue 2 inhibited steady-state current activated by 25 mM NMDA with IC 50 values of 68 and 11 mM, respectively. 3 Reactive blue 2 produced a gradual decline of NMDA-activated current to a steady-state, but this slow onset was not an indication of use-dependence, as it could be eliminated by exposure to reactive blue 2 before NMDA application. In addition, NMDA-activated current recovered completely from inhibition by reactive blue 2 in the absence of agonist. 4 The slow onset of inhibition by reactive blue 2 was not apparently due to an action at an intracellular site, as inclusion of 250 mM reactive blue 2 in the recording pipette did not alter inhibition by 25 mM reactive blue 2 applied externally. 5 Reactive blue 2 and suramin inhibited NMDA-gated channels in a voltage-independent manner. 6 Reactive blue 2, 25 mM, decreased the maximal response to NMDA from 1441 to 598 pA without changing its EC 50 . In contrast, 75 mM suramin increased the EC 50 for NMDA from 13 to 35 mM, and decreased the maximal response to NMDA from 1822 to 1498 pA. Schild analysis of suramin inhibition of NMDA-activated current yielded a nonlinear plot. 7 Both agents decreased the maximal response to glycine without altering its EC 50 . 8 Suramin and reactive blue 2 appear to inhibit NMDA receptor-channels in a manner that is noncompetitive with respect to both NMDA and glycine. However, inhibition by suramin di ered from that by reactive blue 2, in that suramin signi®cantly increased the EC 50 of NMDA.

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Section: Discussionsupporting

confidence: 93%

supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Peoples

1998

British J Pharmacology

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“…It has been found that low concentrations of suramin potentiated ATP‐induced currents at the mouse P2X 4 receptor (Townsend‐Nicholson et al ., 1999), but, as discussed earlier, differences in protocol make comparisons with the present study difficult. Lack of specificity of suramin has also been reported (Balcar et al ., 1995) and the synthesis of more selective P2 receptor antagonists would greatly facilitate the functional characterization of P2X receptors.…”

Section: Discussionmentioning

confidence: 99%

“…(1996) described modest inhibition by suramin. It should be noted that high concentrations of suramin have been shown to have non‐specific effects, and as such cannot be considered as being highly selective for P2 receptors (Balcar, 1995).…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of the P2X₄ receptor orthologues

Jones¹,

Chessell²,

Simon³

et al. 2000

British J Pharmacology

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1 The aim of this study was to functionally characterize the recombinant mouse P2X 4 receptor and to compare its pharmacological properties with those of the human and rat orthologues. 2 Whole cell recordings were made from rafts of HEK-293 cells stably expressing recombinant mouse, rat or human P2X 4 receptors, using Cs-aspartate containing electrodes (3 ± 8 MO) in a HEPES-buered extracellular medium. 3 The agonist potency of ATP at the three species orthologues was similar, with mean EC 50 values of 2.3 mM, 1.4 mM and 5.5 mM, respectively. 4 Adenosine-5'-tetraphosphate (AP4) acted as a partial agonist with respect to ATP at the mouse and human P2X 4 receptors (EC 50 =2.6 and 3.0 mM), but was signi®cantly less potent at the rat orthologue (EC 50 =20.0 mM). a,b-methylene adenosine-5'-triphosphate (a,b-meATP) also acted as a partial agonist, producing 29% of the maximum response at the mouse P2X 4 and 24% at the human P2X 4 receptor. 5 In contrast to the other species orthologues, a,b-meATP failed to elicit a signi®cant agonist response at rat P2X 4 receptors, and was found to act as an antagonist, with an IC 50 of 4.6 mM, against 10 mM ATP. 6 Mouse P2X 4 receptors were found to be sensitive to the antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (IC 50 =10.5 mM), as were human P2X 4 receptors (IC 50 =9.6 mM). The rat receptor however, showed a low sensitivity to PPADS (IC 50 4100 mM). 7 All three orthologues were relatively suramin-insensitive (IC 50 4100 mM) and insensitive to 1-[N,O-Bis(5-isoquinoline sulphonyl)benzyl]-2-(4-phenylpiperazine)ethyl]-5-isoquinoline sulphonamide (KN-62; IC 50 43 mM). 8 Our results suggest that the pharmacological properties of the mouse receptor are most similar to the human P2X 4 receptor, and dier markedly from the rat receptor.

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Suramin inhibits β-bungarotoxin-induced activation of N-methyl-d-aspartate receptors and cytotoxicity in primary neurons

Tseng

Lin‐Shiau

2003

Toxicology and Applied Pharmacology

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Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist, suramin

Cited by 9 publications

References 0 publications

Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Functional characterization of the P2X₄ receptor orthologues

Suramin inhibits β-bungarotoxin-induced activation of N-methyl-d-aspartate receptors and cytotoxicity in primary neurons

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Inhibition of [3H]CGP 39653 binding to NMDA receptors by a P2 antagonist, suramin

Cited by 9 publications

References 0 publications

Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Inhibition of NMDA‐gated ion channels by the P2 purinoceptor antagonists suramin and reactive blue 2 in mouse hippocampal neurones

Functional characterization of the P2X4 receptor orthologues

Suramin inhibits β-bungarotoxin-induced activation of N-methyl-d-aspartate receptors and cytotoxicity in primary neurons

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Functional characterization of the P2X₄ receptor orthologues