Differential effects of propofol and ethanol on P2X4 receptors expressed in Xenopus oocytes

Abstract

The current study investigated the effects of propofol on P2X4 receptors expressed in Xenopus oocytes using two-electrode voltage clamp. We also tested the effects of 100 mM ethanol on the same oocytes used to test propofol. Propofol potentiated ATP-gated currents in a concentration dependent manner in P2X4 receptors. In agreement with our previous findings, ethanol inhibited P2X4 receptors. The opposite effects of propofol and ethanol on P2X4 receptor function suggest that these anesthetics act via different sites/mechanisms in P2X receptors as has been suggested for GABA A and glycine receptors.

Activation and Regulation of Purinergic P2X Receptor Channels

“…Propofol, Ketamine, and Toluene. Propofol, an intravenous anesthetic that is widely used clinically, potentiates the activity of P2X4Rs expressed in HEK293 cells and has no effect on P2X2Rs or P2X2/3Rs (Tomioka et al, 2000;Davies et al, 2005b). Propofol also potentiates native P2X7Rs expressed in microglia, an effect that was mimicked by two other clinically relevant intravenous anesthetics, thiopental and ketamine (Nakanishi et al, 2007).…”

Chronic Cannabis Intoxication and Propofol-Induced Salivation: Causes and Considerations

“…Propofol alone or in combination with another drug has been linked to hypersalivation [23]. Propofol has been shown to increase influx of extracellular calcium into the cytoplasm [24][25][26] by potentiating acinar cell responses to ATP mediated by P2X4 receptors expressed on acinar cells. Because of the significant dependence of salivation on calcium, Propofol's action on cell calcium by these mechanisms may represent a possible mechanism for propofol to increase saliva secretion.…”

Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System Disorders

“…Moreover, a direct link between P2X4 and the regulation of dopamine neurotransmission in the mesolimbic system has been established, further indicating that through its presence in dopaminergic neurons of the mesolimbic system, P2X4 plays a role in mediating alcohol drinking behavior [183] . Interestingly, low ethanol concentrations are able to inhibit P2X4 in vitro, probably by blocking opening of the channel without affecting its deactivation [186,187] . Conversely, ivermectin is able to with the linkage site of ethanol on the P2X4 receptor [188] .…”