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Gene Review

Htr3a  -  5-hydroxytryptamine (serotonin) receptor 3A

Mus musculus

Synonyms: 5-HT-3, 5-HT3 receptor, 5-HT3-A, 5-HT3A, 5-HT3R, ...
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Disease relevance of Htr3a


Psychiatry related information on Htr3a


High impact information on Htr3a


Chemical compound and disease context of Htr3a


Biological context of Htr3a


Anatomical context of Htr3a


Associations of Htr3a with chemical compounds

  • However, WAY-100635, a selective 5-HT1A receptor antagonist, and ramosetron, a selective 5-HT3 receptor antagonist, were not active [25].
  • In addition, the every-other-residue periodicity of the effects on granisetron affinity strongly suggests that this region of the ligand-binding site of the 5HT3R (and by inference, other members of the ligand-gated ion channel family) is in a beta-strand conformation [26].
  • Comparison of the sequences of these two subunits with the 5HT3R shows that a tryptophan residue is found in the homologous position in the 5HT3R (Trp-89), suggesting that this residue may be involved in curare-5HT3R interactions [26].
  • 5-hydroxytryptamine type 3 (5-HT3) receptors are members of the Cys-loop receptor superfamily [27].
  • The response was blocked by 1-10 nM 5-HT3 receptor-specific antagonists MDL 7222 or ICS 205-930, but not by 1 microM 5-HT1/5-HT2 receptor antagonist spiperone or 5-HT2 receptor-specific antagonist ketanserin [28].

Physical interactions of Htr3a


Regulatory relationships of Htr3a

  • The aim of the present study was to examine the influence of ifenprodil (a non-competitive NMDA receptor antagonist which also blocks 5-HT3 receptors and alpha1-adrenoceptors) on the effects of ethanol in the mouse in vivo and to elucidate the role of various receptors in these actions [31].

Other interactions of Htr3a

  • While a fair amount is known about the role of 5-HT1 and 5-HT2 receptor subtypes in regulating these behaviors, much less is known about the involvement of the 5-HT3 receptor, especially with regards to its role in sex differences in behavior [6].
  • The structure of the mouse 5-HT3 receptor gene, 5-HT3R-A, is most similar to nicotinic acetylcholine receptor (nAChR) genes, in particular to the gene encoding the neuronal nAChR subunit alpha 7 [22].
  • The cooperative effect of SP on this 5-HT3-evoked response resulted neither from an interaction of the peptide with the 5-HT3 receptor binding site nor from a possible direct activation of G proteins in NG 108-15 cells [32].
  • 1. The aim of this study was to provide evidence that anpirtoline, which is an agonist at 5-HT1B and 5-HT1D receptors and also displays submicromolar affinity for 5-HT1A recognition sites, in addition, acts as an antagonist at 5-HT3 receptors [33].
  • Throughout the hippocampal formation, CB1 is coexpressed with D2, 5-HT1B and 5-HT3 [34].

Analytical, diagnostic and therapeutic context of Htr3a


  1. Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. Hargreaves, A.C., Lummis, S.C., Taylor, C.W. Mol. Pharmacol. (1994) [Pubmed]
  2. Expression of recombinant homo-oligomeric 5-hydroxytryptamine3 receptors provides new insights into their maturation and structure. Green, T., Stauffer, K.A., Lummis, S.C. J. Biol. Chem. (1995) [Pubmed]
  3. Ca2+ influx through voltage-gated Ca2+ channels regulates 5-HT3 receptor channel desensitization in rat glioma x mouse neuroblastoma hybrid NG108-15 cells. Jones, S., Yakel, J.L. J. Physiol. (Lond.) (1998) [Pubmed]
  4. Orally active benzoxazole derivative as 5-HT3 receptor partial agonist for treatment of diarrhea-predominant irritable bowel syndrome. Yoshida, S., Shiokawa, S., Kawano, K., Ito, T., Murakami, H., Suzuki, H., Sato, Y. J. Med. Chem. (2005) [Pubmed]
  5. Characterization of a mouse serotonin 5-HT3 receptor purified from mammalian cells. Hovius, R., Tairi, A.P., Blasey, H., Bernard, A., Lundström, K., Vogel, H. J. Neurochem. (1998) [Pubmed]
  6. Deletion of the 5-HT3 receptor differentially affects behavior of males and females in the Porsolt forced swim and defensive withdrawal tests. Bhatnagar, S., Nowak, N., Babich, L., Bok, L. Behav. Brain Res. (2004) [Pubmed]
  7. 5-HT(3A) receptor subunit is required for 5-HT3 antagonist-induced reductions in alcohol drinking. Hodge, C.W., Kelley, S.P., Bratt, A.M., Iller, K., Schroeder, J.P., Besheer, J. Neuropsychopharmacology (2004) [Pubmed]
  8. Effects of acute administration of the 5-HT3 receptor antagonist, BRL 46470A, on the behaviour of mice in a two compartment light-dark box and during social interactions in their home cage and an unfamiliar neutral cage. Gao, B., Cutler, M.G. Neuropharmacology (1992) [Pubmed]
  9. Role of 5-HT4 receptors in the mouse passive avoidance test. Galeotti, N., Ghelardini, C., Bartolini, A. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  10. 5-HT3 receptor over-expression decreases ethanol self administration in transgenic mice. Engel, S.R., Lyons, C.R., Allan, A.M. Psychopharmacology (Berl.) (1998) [Pubmed]
  11. Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors. Labarca, C., Nowak, M.W., Zhang, H., Tang, L., Deshpande, P., Lester, H.A. Nature (1995) [Pubmed]
  12. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Maricq, A.V., Peterson, A.S., Brake, A.J., Myers, R.M., Julius, D. Science (1991) [Pubmed]
  13. 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Yakel, J.L., Jackson, M.B. Neuron (1988) [Pubmed]
  14. Functional characterization of two 5-HT3 receptor splice variants isolated from a mouse hippocampal cell line. Glitsch, M., Wischmeyer, E., Karschin, A. Pflugers Arch. (1996) [Pubmed]
  15. Ultrastructure of the 5-hydroxytryptamine3 receptor. Boess, F.G., Beroukhim, R., Martin, I.L. J. Neurochem. (1995) [Pubmed]
  16. Effects of 5-HT3 receptor antagonists on neuroleptic-induced catalepsy in mice. Silva, S.R., Futuro-Neto, H.A., Pires, J.G. Neuropharmacology (1995) [Pubmed]
  17. Agonist and antagonist effects of apomorphine enantiomers on 5-HT3 receptors. van Hooft, J.A., Vijverberg, H.P. Neuropharmacology (1998) [Pubmed]
  18. An ethological study of the effects of buspirone and the 5-HT3 receptor antagonist, BRL 43694 (granisetron) on behaviour during social interactions in female and male mice. Cutler, M.G. Neuropharmacology (1991) [Pubmed]
  19. Cloning and functional expression of an apparent splice variant of the murine 5-HT3 receptor A subunit. Hope, A.G., Downie, D.L., Sutherland, L., Lambert, J.J., Peters, J.A., Burchell, B. Eur. J. Pharmacol. (1993) [Pubmed]
  20. Expression of a serotonin-gated ion channel in embryonic neural and nonneural tissues. Tecott, L., Shtrom, S., Julius, D. Mol. Cell. Neurosci. (1995) [Pubmed]
  21. Pharmacological characterization of 5-hydroxytryptamine3 receptors in murine brain and ileum using the novel radioligand [3H]RS-42358-197: evidence for receptor heterogeneity. Bonhaus, D.W., Wong, E.H., Stefanich, E., Kunysz, E.A., Eglen, R.M. J. Neurochem. (1993) [Pubmed]
  22. Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Werner, P., Kawashima, E., Reid, J., Hussy, N., Lundström, K., Buell, G., Humbert, Y., Jones, K.A. Brain Res. Mol. Brain Res. (1994) [Pubmed]
  23. Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit. Bhattacharya, A., Dang, H., Zhu, Q.M., Schnegelsberg, B., Rozengurt, N., Cain, G., Prantil, R., Vorp, D.A., Guy, N., Julius, D., Ford, A.P., Lester, H.A., Cockayne, D.A. J. Neurosci. (2004) [Pubmed]
  24. The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. Zeitz, K.P., Guy, N., Malmberg, A.B., Dirajlal, S., Martin, W.J., Sun, L., Bonhaus, D.W., Stucky, C.L., Julius, D., Basbaum, A.I. J. Neurosci. (2002) [Pubmed]
  25. S-(+)-fenfluramine-induced nociceptive behavior in mice: Involvement of interactions between spinal serotonin and substance P systems. Tan-No, K., Takahashi, K., Shimoda, M., Sugawara, M., Nakagawasai, O., Niijima, F., Sato, T., Satoh, S., Tadano, T. Neuropeptides (2007) [Pubmed]
  26. Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. Yan, D., Schulte, M.K., Bloom, K.E., White, M.M. J. Biol. Chem. (1999) [Pubmed]
  27. Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Lummis, S.C., Beene, D.L., Lee, L.W., Lester, H.A., Broadhurst, R.W., Dougherty, D.A. Nature (2005) [Pubmed]
  28. Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. Yang, J. J. Gen. Physiol. (1990) [Pubmed]
  29. Novel potent and selective central 5-HT3 receptor ligands provided with different intrinsic efficacy. 1. Mapping the central 5-HT3 receptor binding site by arylpiperazine derivatives. Cappelli, A., Anzini, M., Vomero, S., Mennuni, L., Makovec, F., Doucet, E., Hamon, M., Bruni, G., Romeo, M.R., Menziani, M.C., De Benedetti, P.G., Langer, T. J. Med. Chem. (1998) [Pubmed]
  30. Agonist and antagonist effects of histamine H3 receptor ligands on 5-HT3 receptor-mediated ion currents in NG108-15 cells. Allen, M.C. Eur. J. Pharmacol. (1998) [Pubmed]
  31. Ifenprodil influences changes in mouse behaviour related to acute and chronic ethanol administration. Malinowska, B., Napiórkowska-Pawlak, D., Pawlak, R., Buczko, W., Göthert, M. Eur. J. Pharmacol. (1999) [Pubmed]
  32. Characteristics of [14C]guanidinium accumulation in NG 108-15 cells exposed to serotonin 5-HT3 receptor ligands and substance P. Emerit, M.B., Riad, M., Fattaccini, C.M., Hamon, M. J. Neurochem. (1993) [Pubmed]
  33. 5-HT3 receptor antagonism by anpirtoline, a mixed 5-HT1 receptor agonist/5-HT3 receptor antagonist. Göthert, M., Hamon, M., Barann, M., Bönisch, H., Gozlan, H., Laguzzi, R., Metzenauer, P., Nickel, B., Szelenyi, I. Br. J. Pharmacol. (1995) [Pubmed]
  34. Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Hermann, H., Marsicano, G., Lutz, B. Neuroscience (2002) [Pubmed]
  35. Highly potent inhibitory effects of 5-HT3 receptor antagonist, GR38032F, on non-opioid defeat analgesia in male mice. Rodgers, R.J., Shepherd, J.K., Randall, J.I. Neuropharmacology (1990) [Pubmed]
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