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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low concentrations of ethanol have been found to enhance the electrophysiologic effect of serotonin (5-HT) acting at 5-HT3 receptors on NCB-20 cells. To determine whether this action of ethanol reflects a change in the agonist-receptor interaction, the effect of ethanol (100 mM) on agonist and antagonist binding to 5-HT3 receptor was studied in vitro in membrane from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [3H]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [3H]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [3H]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [3H]GR65630 binding by 5-HT was approximately 30%. Ethanol decreased the affinity of the receptor for 2-methyl-5-HT, but not to 5-HT in NCB-20 cells, and had no effect on agonist binding in brain membranes. The results indicate that enhancement of 5-HT responses at 5-HT3 receptors by ethanol is not a result of changes in the equilibrium binding characteristics of the agonist.
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PMID:Ethanol fails to modify [3H]GR65630 binding to 5-HT3 receptors in NCB-20 cells and in rat cerebral membranes. 175 8

Effects of ethanol on receptor/channel complexes appear to play an important role in acute intoxication. One such receptor that has not previously been investigated for ethanol sensitivity is the 5-HT3 receptor for the neurotransmitter serotonin. Ethanol potentiates ion current mediated by 5-HT3 receptors in NCB-20 neuroblastoma cells and isolated Nodose ganglion neurons examined with whole-cell patch-clamp recording. Potentiation increases in a concentration-dependent manner over a range of concentrations (25-100 mM) achieved during acute intoxication. Potentiation appears to be due to a direct effect on the 5-HT3 receptor. Ethanol's effect on 5-HT3 receptor-mediated current decreases with increasing agonist concentration, providing an initial clue as to the mechanism of ethanol's action. These data are discussed in light of recent behavioral data suggesting a role for 5-HT3 receptors in the discriminative stimulus and reinforcing properties of ethanol.
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PMID:Ethanol potentiates ion current mediated by 5-HT3 receptors on neuroblastoma cells and isolated neurons. 184 35

N1E-115 mouse neuroblastoma cells were used to study the influence of ethanol on the 5-HT- and veratridine-induced influx of 14C-guanidinium via the 5-HT3 receptor channel and the fast sodium channel, respectively. Ethanol (10-100 mM) concentration-dependently increased the 5-HT-induced 14C-guanidinium influx, leaving the basal and veratridine (100 microM)-induced influx unaffected. The increasing effect of ethanol (100 mM) was observed at all 5-HT concentrations investigated; accordingly, ethanol increased the maximum response to 5-HT. Whereas in the absence of ethanol the concentration-response curve for 5-HT was bell-shaped, this was no longer the case when ethanol (100 mM) was present in the incubation buffer; the descending branch of the concentration-response curve for 5-HT at concentrations above 300 microM was virtually no longer observed. When, in the presence of substance P (10 microM) the 5-HT-induced 14C-guanidinium influx was already enhanced, the ability of ethanol (100 mM) to increase the 5-HT-induced influx was considerably diminished (by 72%). Preincubation of N1E-115 cells with 5-HT caused a decay of the subsequent 5-HT response ("desensitization") which was dependent on the duration of preincubation; ethanol (100 mM) did not affect the rate of this decay of the 5-HT response. The 5-HT (30 microM)-induced 14C-guanidinium influx was also increased by methanol (100 mM) and n-propanol (100 mM). The rank order of the increasing effect of the n-alkanols (at 100 mM) was: methanol < ethanol < n-propanol; i.e. the degree of enhancement increased with the lipophilicity of the alcohols.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increasing effect of ethanol on 5-HT3 receptor-mediated 14C-guanidinium influx in N1E-115 neuroblastoma cells. 747 37

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

The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 receptor antagonist ondansetron 10 micrograms/kg i.v. abolished the 5-HT- but not the capsaicin-stimulated bradycardia, indicating that 5-HT and capsaicin acted via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Ethanol at 1.0 and 2.0 g/kg i.p. inhibited in a dose-dependent manner (by 20-45%) the 5-HT- but not the capsaicin-stimulated decrease in heart rate. Our results demonstrate that the inhibitory effect of ethanol on the 5-HT3 receptor-mediated Bezold-Jarisch reflex may be related to the direct effect of ethanol on 5-HT3 receptors on sensory vagal nerves in the heart.
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PMID:Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors. 767 10

One subunit of the 5-hydroxytryptamine3 (5-HT3) receptor has been cloned, and expression of cDNA coding for this protein in Xenopus oocytes results in the formation of homomeric ion channels. In the present study, this system was used to define the sensitivity of the 5-HT3 receptor to alcohols and anesthetics. Ethanol, in pharmacologically relevant concentrations, potentiated 5-HT-mediated currents, with the greatest potentiation observed at lower concentrations of 5-HT. Likewise, butanol stimulated the receptor but with greater efficacy and potency than ethanol. The volatile anesthetics isoflurane, halothane and 1,2,2-trifluorocyclobutane (F3) all enhanced 5-HT3 receptor function. Concentrations of these anesthetics below the minimal alveolar concentration for anesthesia (MAC) produced significant stimulation of 5-HT-mediated currents. Similar to the alcohols, the greatest enhancement of 5-HT3 receptor function by anesthetics was seen at lower concentrations of 5-HT. However, anesthetics were substantially more efficacious than ethanol in enhancing 5-HT3 receptor function. In the presence of 0.5 microM 5-HT, maximal stimulation by ethanol was approximately 50%, but anesthetic enhancement of 5-HT3 receptor-mediated currents did not reach a maximum. Over the concentrations tested, anesthetics potentiated 0.5 microM 5-HT-mediated currents by approximately 25% to 400%. The intravenous anesthetic propofol did not enhance 5-HT3 receptor function or change the potentiation of this receptor by halothane. These results suggest that alcohols and volatile anesthetics have similar actions on 5-HT3 receptor function, which is in agreement with results of studies with other members of the superfamily of ligandgated ion channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. 796 11

Recent studies have suggested that alcohols can affect the function of neurotransmitter-gated ion channels by a direct interaction with the receptor protein. However, the molecular region of the receptor protein that mediates the alcohol action is not known. To address this question, we studied the effect of ethanol on the function of recombinant nicotinic acetylcholine type alpha 7 (nACh alpha 7) receptors, 5-hydroxytryptamine (serotonin) type 3 (5-HT3) receptors, and a chimeric receptor constructed from these two receptors. The receptors were expressed in Xenopus oocytes and their function was studied using the two-electrode voltage-clamp technique. Ethanol inhibited the response of nACh alpha 7 receptors in a concentration-dependent manner over the concentration range of 5-100 mM; the EC50 for this inhibition was 33 mM ethanol. Ethanol decreased the maximal amplitude (Emax) of the nACh alpha 7 receptor agonist concentration-response curve, without significantly affecting the EC50. In contrast, ethanol potentiated 5-HT3 receptor-mediated responses at low agonist concentrations. The potentiation was concentration-dependent over the concentration range of 10-100 mM; the EC50 for this potentiation was 57 mM ethanol. The magnitude of the ethanol potentiation of 5-HT3 receptor-mediated responses decreased with increasing agonist concentration. The chimeric receptor had the amino-terminal domain from the nACh alpha 7 receptor and the transmembrane and carboxyl-terminal domains from the 5-HT3 receptor. Ethanol was found to inhibit the function of this chimeric receptor in a manner similar to that of nACh alpha 7 receptors. Because the inhibition transfers with the amino-terminal domain of the receptor, the observations suggest that the amino-terminal domain of the receptor is involved in the inhibition.
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PMID:Ethanol inhibition of nicotinic acetylcholine type alpha 7 receptors involves the amino-terminal domain of the receptor. 886 48

Ethanol-induced emesis were investigated using Suncus murinus and the emetogenic mechanisms of ethanol were compared with those of cisplatin. Intraperitoneal injection of ethanol caused dose-dependent emesis with ED50 value of 22.3% (v/v) when injection volume was adjusted to 4 ml/kg. Intraperitoneal and subcutaneous injection of acetaldehyde also caused dose-dependent emesis (ED50 = 3.5% (v/v) with an extremely shorter latency (6% i.p.: 1.0 +/- 0.3 min cf. 40% ethanol: 13.0 +/- 1.9 min). Neither ethanol nor acetaldehyde caused emetic responses when injected intracerebroventricularly. Pretreatment with disulfiram, an inhibitor of liver aldehyde dehydrogenase, potentiated the emetogenic effects of ethanol. Surgical abdominal vagotomy, which blocks cisplatin-induced emesis completely, did not prevent ethanol-induced emesis. 5-HT3 receptor antagonists, which also cause complete inhibition of cisplatin-induced emesis, did not affect the responses. However, ethanol-induced emesis was prevented by the pretreatment with 8-hydroxy-2-(di-n-propylamino)tetrarin hydrobromide (8-OH-DPAT) and N-(2-mercaptopropionyl)-glycine (MPG) dose-dependently. The tackykinin NK1 receptor antagonist (+)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl-piperidine (CP-99,994) also attenuated ethanol-induced emesis. Taken together, these results suggest that 1) acetaldehyde is probably responsible for ethanol-induced emesis, 2) active site for ethanol maybe peripheral, 3) ethanol-induced emesis is mediated by free radicals, and 4) mechanism of ethanol-induced emesis and that caused by cisplatin are different in many respects, although in some they are similar and that the precise pathways remain to be identified. Therefore, the tolerance to emetogenic effects of cisplatin in alcoholic patients cannot be explained as a simple cross desensitization of the pathway.
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PMID:Ethanol-induced emesis in the house musk shrew, Suncus murinus. 901 Apr 80

The influence of ethanol on 5-hydroxytryptamine (5-HT)-induced tachycardia mediated by 5-HT3 receptor activation in the isolated guinea-pig atrium was studied. Ethanol at 200 mM significantly inhibited 5-HT - but not isoproterenol- or histamine-induced tachycardia in the isolated guinea-pig atrium. The same inhibitory effect was observed in response to 2-propanol and chloral hydrate application. Both 2-propanol at 100 mM and chloral hydrate at 1 mM exhibited inhibitory effects on 5-HT -induced tachycardia as potent as those of ethanol at 200 mM. These alcohols did not inhibit the tachycardia induced by isoproterenol or histamine. The inhibitory effects of the alcohols seemed to be specific for 5-HT and to increase according to their lipophilicity. Our results suggest that the inhibitory effects of ethanol on 5-HT3 receptor-mediated tachycardia are related to the direct effect of ethanol on 5-HT3 receptors in the atrium.
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PMID:Inhibitory effect of ethanol on the 5-HT3 receptor-mediated tachycardia in isolated guinea-pig atrium. 908 82

The effects of acute treatment with 5-HT3 receptor antagonists, ondansetron and ICS 205-930, on the stimulation of activity induced by ethanol-and cocaine were examined. Ethanol (1.8 or 2 g/kg i.p.) or cocaine (15 mg/kg i.p.) produced a significant increase in locomotor activity (LMA) in DBA/2N mice. Pretreatment with ondansetron or ICS 205-930, in doses ranging from 0.001 to 0.1 mg/kg (s.c), did not modify ethanol or cocaine induced stimulation of activity. In contrast, pretreatment with a 10 micrograms/kg dose of either SCH 23390 or spiperone, a D1 and D2 dopamine (DA) receptor antagonist respectively, completely antagonized the stimulation of LMA induced by ethanol. Similar dose of SCH23390, but not spiperone, blocked the stimulation of activity induced by cocaine. These results indicate that D1 but not D 2 DA receptors play a significant role in cocaine induced hyperactivity whereas both D1 and D2 are involved the locomotor activating effects of ethanol.
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PMID:Effects of 5-HT3, D1 and D2 receptor antagonists on ethanol- and cocaine-induced locomotion. 916 90


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