Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of ethanol, chloral hydrate and trichloroethanol upon the 5-HT3 receptor have been investigated by use of electrophysiological techniques applied to recombinant 5-HT3 receptor subunits (5-HT3R-A or 5-HT3R-As) expressed in Xenopus laevis oocytes. Additionally, the influence of trichloroethanol upon the specific binding of [3H]-granisetron to membrane preparations of HEK 293 cells stably transfected with the murine 5-HT3R-As subunit and 5-HT3 receptors endogenous to NG 108-15 cell membranes was assessed. 2. Ethanol (30-300 mM), chloral hydrate (1-30 mM) and trichloroethanol (0.3-10 mM), produced a reversible, concentration-dependent, enhancement of 5-HT-mediated currents recorded from oocytes expressing either the 5-HT3R-A, or the 5-HT3R-As subunit. 3. Trichloroethanol (5 mM) produced a parallel leftward shift of the 5-HT concentration-response curve, reducing the EC50 for 5-HT from 1 +/- 0.04 microM (n = 4) to 0.5 +/- 0.01 microM (n = 4) for oocytes expressing the 5-HT3R-A. A similar shift, from 2.1 +/- 0.05 microM (n = 11) to 1.3 +/- 0.1 microM (n = 4), was observed in oocytes expressing the 5-HT3R-As subunit. Trichloroethanol (5 mM) had little or no effect upon the maximum current produced by 5-HT for either recombinant receptor. 4. Trichloroethanol (5 mM) similarly reduced the EC50 for 2-methyl-5-HT from 13 +/- 0.4 microM (n = 4) to 4.6 +/- 0.2 microM (n = 4) and from 15 +/- 2 microM (n = 4) to 5 +/- 0.4 microM (n = 4) for oocytes expressing the 5-HT3R-A and 5-HT3R-As subunit respectively. Additionally, trichloroethanol (5 mM) produced a clear enhancement of the maximal current to 2-methyl-5-HT (expressed as a percentage of the maximal current to 5-HT) from 63 +/- 0.7% (n = 4) to 101 +/- 1.6% (n = 4) and from 9 +/- 0.2% (n = 4) to 74 +/- 2% (n = 4) for oocytes expressing the 5-HT3R-A and 5-HT3R-As subunit respectively. 5. Trichloroethanol (2.5 mM) had no effect upon the Kd, or Bmax, of specific [3H]-granisetron binding to membrane homogenates of NG 108-15 cells or HEK 293 cells. Similarly, competition for [3H]-granisetron binding by the 5-HT3 receptor antagonists ondansetron and tropisetron was unaffected. However, competition for [3H]-granisetron binding by the 5-HT3 receptor agonists, 5-HT, 2-methyl-5-HT and phenylbiguanide was enhanced by trichloroethanol (2.5 mM). 6 Unexpectedly, the competition for [3H]-granisetron binding by the 5-HT3 receptor antagonist,quipazine, was enhanced by 2.5 mM trichloroethanol. Quipazine (1 nM-0.3 microM) antagonized 5-HT evoked currents recorded from oocytes expressing the 5-HT3R-A subunit with an IC50 of 18 +/- 3 nM(n = 4). Additionally, quipazine (30 nM-0.3 microM) produced a small inward current which was greatly enhanced by 5 mM trichloroethanol and antagonized by 100 nM ondansetron. Collectively, these observations suggest that quipazine may act as a partial agonist.7. The demonstration that a recombinant homo-oligomeric receptor, expressed in a foreign membrane,retains a sensitivity to alcohols, together with the sequencing of alcohol-insensitive 5-HT3 receptor subunits, may lead to a better definition of the alcohol binding site(s).
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PMID:The interaction of trichloroethanol with murine recombinant 5-HT3 receptors. 754 Dec 81

Trichloroethanol (TCEt) potentiated ion current mediated by 5-hydroxytryptamine (5-HT)3 receptors in isolated adult rat nodose ganglion neurons. The magnitude of potentiation of peak current amplitude increased with increasing TCEt concentrations from 0.5 to 5 mM. The rate of decay of current also increased as a function of TCEt concentration. Steady-state current was unaffected by TCEt at concentrations up to 10 mM. A high concentration of TCEt (25 mM) potentiated peak current but inhibited steady-state current. Potentiation appeared to involve an increase in agonist potency as the magnitude of potentiation of peak current decreased with increasing agonist concentration. Agonist application before TCEt treatment decreased the magnitude of potentiation elicited by 5 mM TCEt. These observations indicate that the potentiating action of TCEt arises from an increase in the efficacy with which 5-HT activates current. TCEt appears to facilitate transitions from closed to open states more readily than transitions from desensitized to open states. These observations are consistent with the hypothesis that 5-HT3 receptor function may contribute to the behavioral pharmacology of alcohols and related sedative/hypnotic agents.
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PMID:Trichloroethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in nodose ganglion neurons from the adult rat. 849 23

1. 5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to analyse effects of alcohols on receptor-channel kinetics in detail. 2. Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20-80% rise time and measured desensitization rate of the current induced by low concentrations (1-2 microM) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had similar effects on the 5-HT3 receptor-induced current. 3. TCEt and ButOH decreased the measured desensitization rate of current induced by 10 microM 5-HT, a maximally effective concentration of agonist. These alcohols also increased the relative amplitude of steady state to peak current induced by 2 or 10 microM 5-HT, indicating a possible decrease in the intrinsic rate of desensitization. 4. TCEt also decreased the deactivation rate of the current activated by 2 microM 5-HT after a short pulse of agonist application. 5. Current sweeps generated by 1 microM 5-HT in the presence or absence of 10 mM TCEt or 100 mM EtOH were well fitted using a modified standard kinetic model derived from the nicotinic acetylcholine receptor. This analysis indicated that potentiation by alcohols could be accounted for by increases in the association rate constant coupled with decreases in the dissociation and desensitization rate constants. 6. This study suggests that alcohols potentiate 5-HT3 receptor-mediated current by both increasing the rate of channel activation and stabilizing the open state by decreasing the rates of channel deactivation and desensitization.
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PMID:Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state. 951 97

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.
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PMID:5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols. 972 27