Effect of inhaled volatile anesthetics on ATP-signal transduction system

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This study was undertaken to examine the effects of volatile anesthetics (VA) on ATP signaltransduction system and clarify the involvement of this system in sites and mechanisms of the anesthetics. The experiments were performed both in vivo and in vitro as following.I. In vivo. 1) Effects of the intracerebroventricular (ICV) administration of P2 antagonits on the minimum alveolar concentration (MAC) of VA in rats. 2) The anesthetic interaction between ATP and NMDA receptor agonists in the rats.II. In vitro. 3) Effects of VA on the ATP binding to P2X receptor in the rat brain crude synaptic membrane. 4) Effects of sevoflurane on the ATP-activated inward current in locus coeruleus neurons in pontine slices of rats. 5) Effects of sevoflurane on the recombirtant P2X receptors expressed in HEK 293 cells.Results: I. In vivo. 1) ICV administration of P2 antagonist decreased the MAC of sevoflurane and isoflurane. 2) The effects of coadministration of both ATP and NMDA receptor antagonists was additive in the reduction of sevoflurane MAC.II. In vitro. 3) VA did not affect the ATP binding to P2X receptor. 4) ATP-activated inward current in locus coeruleus neurons was dose-dependentiy reduced by s-evoflurane. 5) The inward currents through P2X2 and P2X4 receptors were suppressed by sevoflurane in raft but not isolated cells.These results suggest that inhibition of ATP signal transduction system is, at least in part, involved in the site and mechanism of VA's mode of action. Furthermore, suppression of signaling through gap junction is also implicated with the site and mechanism of action of VA.