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This report of the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism highlights the actions of ethanol on purinergic (P2XRs) and 5-hydroxytryptamine 3 (5-HT 3 Rs) receptors. Both P2XRs and 5-HT 3 Rs, are modulated by pharmacologically relevant concentrations of ethanol, with inhibition or stimulation of P2XR subtypes and stimulation of 5-HT 3 Rs, respectively. With regard to ethanol-modulatory actions, these 2 distinctly different receptor classes have been studied to a much lesser extent than other LGICs. The organizers and chairs were Daryl L. Davies and Tina K. Machu. John J. Woodward discusses the molecular pharmacology and physiology of P2XRs and 5-HT 3 Rs and sets the stage for a detailed investigation into the ethanol sensitivity of these channels by the invited speakers. Daryl L. Davies discusses the results from recent electrophysiological studies conducted in his and Dr. Woodward's laboratories, highlighting the actions of ethanol on P2XR subtypes. Jiang-Hong Ye discusses results from recent studies using loose-patch and whole-cell recordings on purinergic receptors expressed on neurons from the ventral tegmental area (VTA) in rats. Tina K. Machu discusses electrophysiological studies conducted in her and Dr. David Lovinger's laboratories on nonpore lining residues of the second transmembrane domain (TM2) of the 5-HT 3A receptor. Li Zhang presents data demonstrating that F-actin cytoskeletons play a critical role in 5-HT 3 receptor clustering in hippocampal neurons. Collectively, the presentations provided strong evidence that P2X and 5-HT 3 receptors are important targets for ethanol action.

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.