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[3H] α,β-methylene ATP binding to P2X purinoceptor is unaffected by volatile anaesthetics

Published online by Cambridge University Press:  23 December 2004

E. Masaki
Affiliation:
Jikei University School of Medicine, Department of Pharmacology, Tokyo, Japan Jikei University School of Medicine, Department of Anesthesiology, Tokyo, Japan
K. Yamazaki
Affiliation:
Jikei University School of Medicine, Department of Internal Medicine, Tokyo, Japan
S. Hori
Affiliation:
Jikei University School of Medicine, Department of Pharmacology, Tokyo, Japan
M. Kawamura
Affiliation:
Jikei University School of Medicine, Department of Pharmacology, Tokyo, Japan
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Abstract

Summary

Background and objective: The P2X receptor is responsible for fast excitatory neurotransmission in the central nervous system. This receptor is suggested as one of the targets of volatile anaesthetics. The study was undertaken to examine the site of action of volatile anaesthetics, especially for P2X purinoceptor-mediated neurotransmission.

Methods: The effect of sevoflurane and isoflurane on [3H] α,β-methylene ATP binding was investigated in rat crude synaptic membranes. The crude synaptic membranes were prepared from Sprague-Dawley rat brains by centrifugation and then incubated with volatile anaesthetics or P2 receptor antagonists.

Results: [3H] α,β-methylene ATP binding was unchanged by either sevoflurane or isoflurane at clinically relevant concentrations. Suramin, a P2 antagonist, significantly (P < 0.05) decreased the binding of [3H] α,β-methylene ATP in a dose-dependent manner (68.7 ± 14.7% at 10 μmol, 49.5 ± 6.4% at 50 μmol, 24.3 ± 5.7% at 100 μmol, n = 10, mean ± SD), whereas pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), another P2 antagonist, did not affect the binding.

Conclusions: The suppressive effect of volatile anaesthetics on ATP-mediated excitatory synaptic transmission could be one site of action. However, the blockade of ATP binding to P2X receptors is not a mechanism of action of volatile anaesthetics.

Type
Original Article
Copyright
2004 European Society of Anaesthesiology

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