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)

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

The involvement of 5-hydroxytryptamine (5-HT) in gastric function and mucosal damage has been defined. 5-HT also potentiates lesion formation in animals. The current study investigated further whether these actions are mediated through 5-HT3 receptors in rats. Ondansetron, a 5-HT3 receptor antagonist, was given subcutaneously, 2 or 4 mg/kg, 30 min before the gastric parameters were measured. The higher dose of ondansetron, 4 mg/kg, significantly increased gastric mucosal blood flow (GMBF) and also basal acid and Na+ secretion. However, it did not affect pepsin output. 5-HT time dependently reduced GMBF and pepsin secretion, but not that of acid and Na+. These actions were not altered by ondansetron pretreatment. The drug, however, dose dependently reduced ethanol-induced gastric mucosal lesions in the 5-HT-treated animals. These findings indicate that 5-HT3 receptors regulate not only basal GMBF, but also acid and Na+ secretion in stomachs. However, the depressive action of 5-HT on GMBF and pepsin secretion is most likely not mediated through 5-HT3 receptors. Ondansetron also modulates the toxicities of ethanol in the stomach and this action is likely to be mediated through the preservation of GMBF.
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PMID:Modulatory role of 5-HT3 receptors in gastric function and ethanol-induced mucosal damage in rat stomachs. 797 27

Arginine8-vasopressin (AVP) has been shown repeatedly to affect learning and memory and to maintain tolerance to ethanol if the brain serotonin and catecholamine systems are intact. In the present study, 5,7-dihydroxytryptamine (5,7-DHT) was injected intracerebroventricularly to disrupt serotonergic projections from the raphe to the forebrain. This resulted in a marked decrease in 5-hydroxytryptamine (5-HT) immunoreactivity in the terminal areas of the septum and the hippocampus, but not in the serotonin-containing neuronal cell bodies in the raphe nuclei. In control rats, tolerance to the motor-impairing effects of ethanol lasted for only 5 days after the cessation of ethanol treatment but could be maintained indefinitely for as long as AVP was given. In the 5,7-dihydroxytryptamine-lesioned rats, AVP was unable to maintain the tolerance. Continuous intracerebroventricular infusion of 5-HT restored the ability of AVP to maintain ethanol tolerance in the lesioned rats. A selective 5-HT2 agonist (alpha-methylserotonin) was equally effective, and a 5-HT3 receptor agonist (2-methylserotonin) was slightly less effective, but the 5-HT1A agonist dipropylaminotetralin (8-hydroxy-dipropylaminotetralin) was totally ineffective in this respect. The results indicate selective involvement of brain 5-HT2 and possibly 5-HT3 receptors in mediating AVP maintenance of tolerance to ethanol but do not pinpoint their specific loci or roles.
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PMID:Selective involvement of central 5-HT2 receptors in the maintenance of tolerance to ethanol by arginine8-vasopressin. 807 72

Recent evidence suggests that central 5-HT3 are intimately involved in the ethanol (ETOH) dependence mechanism. In the present study we observed the effects of the 5-HT3 receptor antagonist ICS 205-930 on audiogenic seizure response (ASR) in ETOH-withdrawn rats and on ETOH intake and preference. Low doses of ICS 205-930 (0.001 mg/kg), but not higher doses (0.1 mg/kg), markedly reduced both ASR and ETOH intake in a high preference group of animals. The possible mechanism of different effects of low and high drug doses is discussed.
Alcohol
PMID:The abilities of 5-HT3 receptor antagonist ICS 205-930 to inhibit alcohol preference and withdrawal seizures in rats. 821 82

The effect of 5-HT3 receptor antagonists such as ondansetron, ICS 205-930, MDL 72222, metoclopramide, and zacopride was investigated on the ethanol as well as diazepam withdrawal phenomena in the present study. There was a significant increase in locomotor activity in the ethanol- as well as diazepam-withdrawn rats. The treatment of rats with 5-HT3 receptor antagonists during withdrawal phase did not modify the effect. The ethanol-withdrawn rats were more sensitive to pentylenetetrazole (PTZ)-induced convulsions as compared to control animals. 5-HT3 receptor antagonists did not attenuate the increased sensitivity of ethanol-withdrawn rats to PTZ. These observations indicated that 5-HT3 receptor antagonists are ineffective in attenuating hyperlocomotor activity following abrupt termination of chronic administration of ethanol or diazepam, and increased sensitivity to PTZ in the ethanol-withdrawn rats.
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PMID:Ethanol- and diazepam-withdrawal hyperlocomotion is not due to 5-HT3 receptor stimulation. 833 36

We tested how 5-HT3 receptor antagonists, tropisetron (TR) and ondansetron (ON) affect the hyperlocomotion induced by single dose of ethanol EtOH) in mice. EtOH in a dose-dependent manner (0.5-2.0 g/kg ip) increased locomotion of mice. The effect of 2.0 g/kg of EtOH was reduced by ON (0.1 mg/kg and 1.0 mg/kg sc) and, to the lesser extent and only in limited dose range (0.01 mg/kg) by TR. Tropisetron (but not ON) increased concentrations of EtOH in the blood. The data suggest that 5-HT3 receptor is involved in EtOH-induced hyperlocomotion.
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PMID:Effects of 5-HT3 receptor antagonists on ethanol-induced hyperlocomotion in mice. 861 7

In rats vertically implanted with concentric dialysis probes in the medial prefrontal cortex and in the medial nucleus accumbens, morphine, ethanol and nicotine failed to modify extracellular dopamine in the medial prefrontal cortex at doses that were fully effective in raising extracellular dopamine in the nucleus accumbens. Conversely, the aversive/anxiogenic drugs picrotoxin, pentylenetetrazol and FG 7142, administered at subconvulsant doses, increased extracellular dopamine in the medial prefrontal cortex but failed to do so in the nucleus accumbens. Systemic administration of low doses of the 5HT3 antagonist ICS 205930, previously reported to prevent the increase of extracellular dopamine in the nucleus accumbens elicited by morphine, nicotine, ethanol and haloperidol (Carboni et al. 1989) as well as by stress (Imperato et al. 1990), also prevented the increase of extracellular dopamine elicited in the prefrontal cortex by anxiogenic drugs. Therefore, mesocortical and mesolimbic dopamine neurons show clear-cut differences in the reactivity to drugs of abuse and to aversive drugs but are both modulated by a facilitatory serotonergic input mediated by 5HT3 receptors.
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PMID:Non-psychostimulant drugs of abuse and anxiogenic drugs activate with differential selectivity dopamine transmission in the nucleus accumbens and in the medial prefrontal cortex of the rat. 873 43

We have examined the actions of alkanols, halogenated ethanol derivatives and diethyl ether on ion current mediated by 5-HT3 receptors in NCB-20 neuroblastoma cells. The alcohols and diethyl ether potentiated 5-HT3 receptor-mediated ion current at concentrations that had no effect on membrane current when applied in the absence of agonist. The potency of alcohols increased with increasing hydrophobicity. However, the maximal efficacy of alcohols was unrelated to hydrophobicity. Interactions between different drugs applied simultaneously to cells were examined to determine whether these compounds compete for a distinct modulatory site associated with the 5-HT3 receptor. Analysis of interactions observed at different drug concentrations indicated a variety of interactions between different compounds, ranging from negative to positive allosteric interactions. Interactions between trichloroethanol (TCEt) and isopentanol exhibited characteristics that might indicate competition for a single site of action. However, further examination of interactions between these two drugs indicated that although isopentanol altered the efficacy of co-applied TCEt, TCEt did not have a similar effect with respect to isopentanol. Furthermore, isopentanol did not alter the potency of TCEt for potentiation of receptor function. The absence of competitive interactions among alcohols indicates that a single "alcohol receptor" cannot be defined using established pharmacologic approaches. Our findings are most consistent with the idea that alcohols interact with several hydrophobic sites associated with the 5-HT3 receptor.
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PMID:Pharmacologic characteristics of potentiation of 5-HT3 receptors by alcohols and diethyl ether in NCB-20 neuroblastoma cells. 876 25

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

The drug discrimination test was used to evaluate the role of 5-HT3 receptors in the mediation of the stimulus properties of ethanol in rats trained to discriminate between ethanol (1.0 g/kg, 10% v/v, i.p.) and saline vehicle. Rats trained to discriminate between a lower dose of ethanol (0.5 g/kg i.p.) failed to attain discrimination criteria after 20 weeks (100 sessions) of training. None of the doses of 5-HT3 receptor antagonists (0.001, 0.01, 0.1, 1.0, 10.0 mg/kg of tropisetron or ondansetron) administered i.p. 30 min before ethanol, antagonized the discriminative stimulus properties of ethanol. Furthermore, none of the centrally (1, 10, 35 micrograms per rat) or i.p. (0.1, 1.0, 2.5, 5.0, 10.0 mg/kg) administered doses of 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide, could replace the ethanol discriminative cue. These results suggest that 5-HT3 receptors are not primarily involved in the mediation of the stimulus properties of ethanol.
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PMID:Studies on the role of 5-HT3 receptors in the mediation of the ethanol interoceptive cue. 887 32


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