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)

The wild-type and a mutant 5-HT3 receptor were expressed in Xenopus oocytes to further explore how the rate of onset of desensitization of the 5-HT3 receptor was dependent on membrane voltage and primary structure of the channel. The rapid application of serotonin (5-HT; 50 microM) in a Ca(2+)-containing (1.8 mM) bathing solution elicited inward currents that decayed rapidly and with a biphasic time course in most cases. For oocytes expressing the wild-type 5-HT3 receptor and held at a potential of -90 mV, the value of the fast time constant of decay (tau fast) was 0.79 +/- 0.3 s (n = 7), while tau slow was 16 +/- 3 s; the area of the decay phase contributed by tau fast (i.e., Afast) was 50 +/- 4% and Aslow was 38 +/- 5%, with a remainder (i.e., non-desensitizing component) of 12%. The kinetics of the decay phase were strongly voltage-dependent. At a holding potential of -30 mV, the desensitization decay phase was now monophasic, with a time constant of 14.0 +/- 3.1 s (n = 4). Mutating the leucine at position 286 of the wild-type 5-HT3 receptor to threonine (i.e., mutant L286T) resulted in desensitization kinetics that were biphasic at all membrane potentials tested and with a rate of decay that was not voltage dependent. Therefore, desensitization is a multifaceted and complex process, whose rate of onset depends in part to membrane voltage and primary structure of the ion channel.
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PMID:Desensitization of 5-HT3 receptors expressed in Xenopus oocytes: dependence on voltage and primary structure. 878 16

In this study of the amino acid nutrition of a marsupial we tested three hypotheses: (a) that brushtail possums eat less when diets contain excesses or deficiencies in essential amino acids, (b) that brushtail possums choose diets that do not contain amino acid excesses, and (c) that amino acid consumption is mediated partly by the 5HT3 receptor. Possums ate less when 0.2-1.0% methionine (wet matter) was added to the diet, but similar concentrations of lysine and threonine had little effect. However, when given a choice, possums always selected the basal ration over one with added lysine, methionine or threonine at concentrations between 0.05% and 0.9%. In contrast to the experiments with excess amino acids, possums did not eat less of a diet almost devoid of an essential amino acid. Instead, the possums ate less when their diets contained synthetic amino acids rather than similar amounts and proportions of amino acids as casein. Contrary to the third hypothesis, the 5HT3 receptor antagonist, ondansetron, did not affect feeding by possums given a diet containing 0.8% methionine, suggesting that post-ingestive feedback, via the 5HT3 receptor, does not regulate amino acid intake when diets contain amino acid excesses.
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PMID:The effect of excesses and deficiencies in amino acids on the feeding behaviour of the common brushtail possum (Trichosurus vulpecula). 1235 29

The effects of phorbol 12-myristate, 13-acetate (PMA) on 5-hydroxytryptamine (5-HT)-evoked ion currents in the mouse 5-HT3A receptor were examined. Perfusion with PMA caused a concentration dependent potentiation of 5-HT mediated currents and increased both potency and efficacy of 5-HT at the 5-HT3A receptor expressed in Xenopus oocytes. Enhancement of receptor function was partially blocked by injection of oocytes with PKCI, the peptide inhibitor of protein kinase C (PKC). Mutation of all 12 intracellular serine and threonine residues to alanine was without effect on PMA-induced potentiation of 5-HT elicited currents. Mutation of tyrosine 458 in the 5-HT3A receptor lacking intracellular serines and threonines reduced the PMA-induced potentiation of 5-HT evoked currents by approximately 55%. In contrast, mutation of tyrosine 458 in the wild-type receptor did not alter PMA-induced enhancement. The tyrosine kinase inhibitor, lavendustin A, reduced the enhancement of 5-HT3A receptor mediated currents by PMA in the mutant 5-HTA3A receptor containing no intracellular serine or threonine residues, but not in the wild-type receptor. Thus, the role of intracellular serines and threonines is redundant with that of tyrosine, suggesting that these two components act through a similar pathway in response to PMA treatment.
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PMID:Enhancement of 5-hydroxytryptamine3A receptor function by phorbol 12-myristate, 13-acetate is mediated by protein kinase C and tyrosine kinase activity. 1244 87

Previously, we reported that the GABA(A) receptor antagonist picrotoxin also antagonizes serotonin (5-HT)3 receptors and that its effects are subunit-dependent. Here, we sought to identify amino acids involved in picrotoxin inhibition of 5-HT3 receptors. Mutation of serine to alanine at the transmembrane domain 2 (TM2) 2' position did not affect picrotoxin (PTX) sensitivity in murine 5-HT3A receptors. However, mutation of the 6' TM2 threonine to phenylalanine dramatically reduced PTX sensitivity. Mutation of 6' asparagine to threonine in the 5-HT3B subunit enhanced PTX sensitivity in heteromeric 5-HT3A/3B receptors. Introduction of serine (native to the human 3B subunit) at the 6' position also increased PTX sensitivity, suggesting a species-specific effect. Mutation of the 7' leucine to threonine in 5-HT3A receptors increased PTX sensitivity roughly 10-fold, comparable with that observed in GABA(A) receptors, and also conferred distinct gating kinetics. The equivalent mutation in the 3B subunit (i.e., 7' valine to threonine) had no impact on PTX sensitivity in 5-HT3A/3B receptors. Interestingly, [3H]ethynylbicycloorthobenzoate ([3H]EBOB), a high-affinity ligand to the convulsant site in GABA(A) receptors, did not exhibit specific binding in 5-HT3A receptors. The structurally related compound, tert-butylbicyclophosphorothionate (TBPS), which potently inhibits GABA(A) receptors, did not inhibit 5-HT3 currents. Our results indicate that the TM2 6' residue is a common determinant of PTX inhibition of both 5-HT3 and GABA(A) receptors and demonstrate a role of the 7' residue in PTX inhibition. However, lack of effects of EBOB and TBPS in 5-HT3A receptors suggests that the functional domains in the two receptors are not equivalent and underscores the complexity of PTX modulation of LGICs.
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PMID:Molecular determinants of picrotoxin inhibition of 5-hydroxytryptamine type 3 receptors. 1581 70