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Gene Review

Htr3a  -  5-hydroxytryptamine (serotonin) receptor...

Rattus norvegicus

Synonyms: 5-HT-3, 5-HT3, 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

  • Radioligand binding studies show a high density of 5-HT3 receptors in the cholinergic-rich entorhinal cortex and we provide evidence that a reduction in cortical cholinergic function can be effected in vitro by 5-HT3 receptors [11].
  • 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue [11].
  • Selective antagonists for the 5-HT3 receptor subtypes which seem to have effects on mood and activity may exert their effect through the regulation of acetylcholine release in the cortex and limbic system [11].
  • Recently, GR38032F, MDL 72222 and ICS 205-930 have been shown to have behavioural effects in rodents and primates that undoubtedly reflect an action in the central nervous system (refs 9-11 and unpublished observations), suggesting the existence of 5-HT3 receptors in the brain [12].
  • Using these models, selective 5-HT3 receptor antagonists such as MDL 72222 (ref. 5), ICS 205-930 (ref. 6), GR38032F (ref. 7) and BRL 43694 (ref. 8) have been developed [12].

Chemical compound and disease context of Htr3a


Biological context of Htr3a


Anatomical context of Htr3a


Associations of Htr3a with chemical compounds

  • These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT3 receptors [20].
  • However, activation of 5-HT3- or CB1-receptors are likely to have opposing regulatory effects on GABA neurotransmission, as 5-HT3 receptor activation by serotonin results in the release of GABA, while CB1 activation by cannabinoids results in inhibition of GABA release [19].
  • This excitatory response to 5-HT3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation [20].
  • These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by nonserotonergic mechanisms [21].
  • Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats [22].

Physical interactions of Htr3a

  • Under such conditions, cortical 5-HT2 receptor binding sites as well as striatal 5-HT3 and dopamine-related binding sites remained unaltered [23].
  • Most of the synthesized compounds exhibited moderate-to-very high affinity (in many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor [24].

Regulatory relationships of Htr3a

  • The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) [18].
  • 6. The contractile response to GR43175 in the dog isolated saphenous vein was selectively antagonized by methiothepin but was resistant to antagonism by the 5-HT2 receptor blocking drug ketanserin and the 5-HT3 receptor blocking drug MDL 72222 [25].
  • Gastric distension enhances CCK-induced Fos-like immunoreactivity in the dorsal hindbrain by activating 5-HT3 receptors [26].
  • These data suggest that 5-HT4 receptor activation enhances the ability of 5-HT3 receptor activation to induce intestinal allodynia [27].
  • These results suggest that 5-HT3 receptor activation may be required for amphetamine-induced expression of ATF-1-regulated target genes in the striatum, which may include c-Fos [28].

Other interactions of Htr3a


Analytical, diagnostic and therapeutic context of Htr3a

  • PCR experiments, with specific primers located upstream and downstream of the GSLLP deletion, were used to detect reverse transcribed 5-HT3 R-A mRNAs [15].
  • We report the nucleotide and deduced amino acid sequences of a nearly complete rat 5-HT3 receptor subunit and use the sequence to develop a reverse transcription-polymerase chain reaction (RT-PCR) assay that measures 5-HT3 mRNA [33].
  • In this study, we report the presence and distribution of 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum using immunofluorescence histochemistry [30].
  • Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT1A, 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models [34].
  • Finally, central 5-HT1 and/or 5-HT2, but not 5-HT3, receptors may underlie the suppressant effects of dexfenfluramine on heroin self-administration [35].


  1. Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during gut anaphylaxis. Mourad, F.H., O'Donnell, L.J., Ogutu, E., Dias, J.A., Farthing, M.J. Gut (1995) [Pubmed]
  2. The mechanism by which epinastine stops an adenosine analog from contracting BDE rat airways. Meade, C.J. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  3. Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides. Youssefyeh, R.D., Campbell, H.F., Airey, J.E., Klein, S., Schnapper, M., Powers, M., Woodward, R., Rodriguez, W., Golec, S., Studt, W. J. Med. Chem. (1992) [Pubmed]
  4. 5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery. Tokunaga, A., Saika, M., Senba, E. Pain (1998) [Pubmed]
  5. Behavioural effects of serotonin agonists and antagonists in the rat and marmoset. Elliott, P.J., Walsh, D.M., Close, S.P., Higgins, G.A., Hayes, A.G. Neuropharmacology (1990) [Pubmed]
  6. Effects of serotonergic agents on apomorphine-induced locomotor activity. Young, K.A., Zavodny, R., Hicks, P.B. Psychopharmacology (Berl.) (1993) [Pubmed]
  7. A mechanism of 5-HT3 receptor mediation is involved etiologically in the psychological stress lesion the stomach of the mouse. Nomura, K., Maeda, N., Yoshino, T., Yamaguchi, I. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  8. Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists. Shearman, G.T., Tolcsvai, L. Psychopharmacology (Berl.) (1987) [Pubmed]
  9. Prevention by the 5-HT3 receptor antagonist, ondansetron, of morphine-dependence and tolerance in the rat. Hui, S.C., Sevilla, E.L., Ogle, C.W. Br. J. Pharmacol. (1996) [Pubmed]
  10. The role of 5-HT3 receptors in drug dependence. Grant, K.A. Drug and alcohol dependence. (1995) [Pubmed]
  11. 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue. Barnes, J.M., Barnes, N.M., Costall, B., Naylor, R.J., Tyers, M.B. Nature (1989) [Pubmed]
  12. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Kilpatrick, G.J., Jones, B.J., Tyers, M.B. Nature (1987) [Pubmed]
  13. 5-Hydroxytryptamine (5-HT)2 receptor involvement in acute 5-HT-evoked scratching but not in allergic pruritus induced by dinitrofluorobenzene in rats. Nojima, H., Carstens, E. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  14. Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors. Mazzola-Pomietto, P., Aulakh, C.S., Wozniak, K.M., Murphy, D.L. Psychopharmacology (Berl.) (1996) [Pubmed]
  15. Developmental changes in the differential expression of two serotonin 5-HT3 receptor splice variants in the rat. Miquel, M.C., Emerit, M.B., Gingrich, J.A., Nosjean, A., Hamon, M., el Mestikawy, S. J. Neurochem. (1995) [Pubmed]
  16. Cardiovascular effects of 5HT2 and 5HT3 receptor stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats. Merahi, N., Laguzzi, R. Brain Res. (1995) [Pubmed]
  17. Descending serotonergic facilitation mediated through rat spinal 5HT3 receptors is unaltered following carrageenan inflammation. Rahman, W., Suzuki, R., Rygh, L.J., Dickenson, A.H. Neurosci. Lett. (2004) [Pubmed]
  18. 5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons. Férézou, I., Cauli, B., Hill, E.L., Rossier, J., Hamel, E., Lambolez, B. J. Neurosci. (2002) [Pubmed]
  19. Coexistence of serotonin 3 (5-HT3) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus. Morales, M., Bäckman, C. Hippocampus. (2002) [Pubmed]
  20. The role of central 5-HT3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats. Jeggo, R.D., Kellett, D.O., Wang, Y., Ramage, A.G., Jordan, D. J. Physiol. (Lond.) (2005) [Pubmed]
  21. Effects of various serotonin receptor subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats. Aulakh, C.S., Hill, J.L., Murphy, D.L. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  22. Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats. Carvalho, F., Macêdo, D., Bandeira, I., Maldonado, I., Salles, L., Azevedo, M.F., Rocha, M.A., Fregoneze, J.B., De Castro-e-Silva, E. Horm. Metab. Res. (2002) [Pubmed]
  23. Irreversible blockade of central 5-HT1A receptor binding sites by the photoaffinity probe 8-methoxy-3'-NAP-amino-PAT. Emerit, M.B., Gozlan, H., Marquet, A., Hamon, M. Eur. J. Pharmacol. (1986) [Pubmed]
  24. Benzimidazole derivatives. Part 1: Synthesis and structure-activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists. López-Rodríguez, M.L., Benhamú, B., Viso, A., Morcillo, M.J., Murcia, M., Orensanz, L., Alfaro, M.J., Martín, M.I. Bioorg. Med. Chem. (1999) [Pubmed]
  25. GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Humphrey, P.P., Feniuk, W., Perren, M.J., Connor, H.E., Oxford, A.W., Coates, L.H., Butina, D. Br. J. Pharmacol. (1988) [Pubmed]
  26. Gastric distension enhances CCK-induced Fos-like immunoreactivity in the dorsal hindbrain by activating 5-HT3 receptors. Hayes, M.R., Covasa, M. Brain Res. (2006) [Pubmed]
  27. 5-HT4 receptor antagonism potentiates inhibition of intestinal allodynia by 5-HT3 receptor antagonism in conscious rats. Smith, M.I., Banner, S.E., Sanger, G.J. Neurosci. Lett. (1999) [Pubmed]
  28. 5-HT3 receptor activation is required for induction of striatal c-Fos and phosphorylation of ATF-1 by amphetamine. Genova, L.M., Hyman, S.E. Synapse (1998) [Pubmed]
  29. Influence of catecholaminergic and serotonergic receptor antagonists on the hyperglycaemic response to the neuroglucopaenic agent, 2-deoxy-D-glucose. Baudrie, V., Chaouloff, F. Neuropharmacology (1991) [Pubmed]
  30. Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum. Geurts, F.J., De Schutter, E., Timmermans, J.P. J. Chem. Neuroanat. (2002) [Pubmed]
  31. Characterization of the biphasic blood pressure response to alpha-methyl-5-hydroxytryptamine in anaesthetized rats. Balasubramaniam, G., Lee, H.S., Mah, S.C. Archives internationales de pharmacodynamie et de thérapie. (1995) [Pubmed]
  32. Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon. Morales, M., Wang, S.D., Diaz-Ruiz, O., Jho, D.H. J. Comp. Neurol. (2004) [Pubmed]
  33. Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit. Isenberg, K.E., Ukhun, I.A., Holstad, S.G., Jafri, S., Uchida, U., Zorumski, C.F., Yang, J. Neuroreport (1993) [Pubmed]
  34. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. McBride, W.J., Li, T.K. Critical reviews in neurobiology. (1998) [Pubmed]
  35. Further studies to examine the nature of dexfenfluramine-induced suppression of heroin self-administration. Wang, Y., Joharchi, N., Fletcher, P.J., Sellers, E.M., Higgins, G.A. Psychopharmacology (Berl.) (1995) [Pubmed]
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