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

British Journal of Pharmacology
R W Peoples, C Li

Abstract

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 microM NMDA with IC50 values of 68 and 11 microM, 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 microM reactive blue 2 in the recording pipette did not alter inhibition by 25 microM 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 microM, decreased the maximal response to NMDA from 1441 to 598 pA without changing its EC50. In contrast, 75 microM suramin increased the EC50 for NMDA from 13 to 35 microM, and decrea...Continue Reading

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Citations

May 13, 2006·Pflügers Archiv : European journal of physiology·Simon Hussl, Stefan Boehm
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Jul 20, 2011·Purinergic Signalling·Xianmin SongGeoffrey Burnstock
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