5-HYDROXYTRYPTAMINE(3) (5-HT3) RECEPTOR-MEDIATED DEPOLARIZATION OF THE RAT ISOLATED VAGUS NERVE - MODULATION BY TRICHLOROETHANOL AND RELATED ALCOHOLS

The ability of 2,2,2-trichloroethanol (TCE) and related alcohols to mo dify the 5-hydroxytryptamine(3) (5-HT3) receptor-mediated depolarisati on of the rat isolated cervical vagus nerve were investigated by extra cellular electrophysiological recording using the 'grease gap' techniq ue. TCE at millimolar concentrations increased the magnitude of the 5- HT3, receptor-mediated depolarisations of the rat vagus nerve by a num ber of agonists (5-HT, phenylbiguanide (PBG), quipazine). Concentratio n response curves generated for the 5-HT3, receptor agonists, 5-HT and PEG, in the absence and presence of TCE (5 mM) indicated that the pot entiation in agonist-induced depolarisation was due to an increase in both agonist potency and apparent efficacy. Following apparent complet e 5-HT3, receptor desensitisation (induced by either 5-HT or PEG; 100 mu M for 90 min), application of TCE (5 mM) in the continued presence of either agonist induced a depolarisation of the vagus nerve. In addi tion to TCE, a number of related alcohols (tribromoethanol, isopentano l and 5-chloropentanol but not ethanol) at millimolar concentrations a lso potentiated depolarisation of the vagus nerve induced by 5-HT. Com bined application of both TCE (0.1-20 mM) and isopentanol (20 mM) indi cated that the potentiation of the 5-HT3, receptor-mediated depolarisa tion by these alcohols was not additive. The present studies indicate that the 5-HT3 receptor expressed on the cervical vagus nerve is susce ptible to allosteric modulation by a number of alcohols including the anaesthetic agent TCE. Such an interaction may have relevance to the n ausea and vomiting experienced by some patients following recovery fro m general anaesthesia. (C) 1998 Elsevier Science B.V. All rights reser ved.