title: 5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols.
abstract: The ability of 2,2,2-trichloroethanol (TCE) and related alcohols to modify the 5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated cervical vagus nerve were investigated by extracellular electrophysiological recording using the 'grease gap' technique. TCE at millimolar concentrations increased the magnitude of the 5-HT3 receptor-mediated depolarisations of the rat vagus nerve by a number of agonists (5-HT, phenylbiguanide (PBG), quipazine). Concentration response curves generated for the 5-HT3 receptor agonists. 5-HT and PBG, in the absence and presence of TCE (5 mM) indicated that the potentiation in agonist-induced depolarisation was due to an increase in both agonist potency and apparent efficacy. Following apparent complete 5-HT3 receptor desensitisation (induced by either 5-HT or PBG; 100 microM for 90 min), application of TCE (5 mM) in the continued presence of either agonist induced a depolarisation of the vagus nerve. In addition to TCE, a number of related alcohols (tribromoethanol, isopentanol and 5-chloropentanol but not ethanol) at millimolar concentrations also potentiated depolarisation of the vagus nerve induced by 5-HT. Combined application of both TCE (0.1-20 mM) and isopentanol (20 mM) indicated that the potentiation of the 5-HT3 receptor-mediated depolarisation by these alcohols was not additive. The present studies indicate that the 5-HT3 receptor expressed on the cervical vagus nerve is susceptible to allosteric modulation by a number of alcohols including the anaesthetic agent TCE. Such an interaction may have relevance to the nausea and vomiting experienced by some patients following recovery from general anaesthesia.
authors.affiliation: Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Bentley
authors.forename: N M
authors.initials: NM
authors.lastname: Barnes
mesh_terms: D000818:Animals; D002728:Chlorohydrins / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000031:analogs & derivatives / Q000494:pharmacology; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D000439:Pentanols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*
chemical_list: D002728:Chlorohydrins; D007211:Indoles; D000439:Pentanols; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C062527:tribromoethanol; D000431:Ethanol; C115198:5-chloropentanol; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; C029683:isopentyl alcohol; C082871:GR 113808