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Gene Review

Htr2a  -  5-hydroxytryptamine (serotonin) receptor...

Rattus norvegicus

Synonyms: 5-HT-2, 5-HT-2A, 5-HT2A, 5-hydroxytryptamine receptor 2A, 5Ht-2, ...
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Disease relevance of Htr2a


Psychiatry related information on Htr2a

  • In spite of its high affinity for the 5-HT 2A receptor, methysergide only slightly elevated the pain threshold in the hyperalgesic hind limb [2].
  • The role of 5-HT1, 5-HT2 and 5-HT3 receptors in the genesis of colonic motor alterations induced by emotional stress was evaluated in rats equipped with implanted nickel/chrome electrodes on the proximal colon and a catheter into the lateral ventricle of the brain [3].
  • Like hallucinogenic 5-HT2 agonists, LSD (d-lysergic acid diethylamide) produces characteristic decreases in locomotor activity and investigatory behaviors of rats tested in a novel environment [6].
  • The present experiments investigated the effects of agents acting at serotonin (5-HT)-2 receptors on the performance of rats in a choice serial reaction time (5-CSRT) task in order to examine the role of 5-HT2 receptors in the modulation of attention and response control [7].
  • Behavioral experiments, including mescaline- and 5-hydroxytryptophan-induced head twitches and learned helplessness, as well as sleep-waking cycle and EEG spectral parameter studies, indicated that SR 46349B has a classical 5-HT2 psychopharmacological antagonist profile [8].

High impact information on Htr2a

  • Binding studies with appropriate labelled ligands have revealed the existence of two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the central nervous system of mammals [9].
  • Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements [10].
  • The inhibitory effects of the 5-HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ICS 205-930 were studied in cholera toxin- and 5-HT-induced fluid secretion [11].
  • Ketanserin: a selective antagonist of 5-HT2 serotoninergic receptors [12].
  • After expression of this receptor in Xenopus oocytes, the application of serotonin triggered the typical chloride current which presumably results from the activation of phospholipase C. The coupling to this response system was less efficient than that of the 5-HT1C or 5-HT2 receptors [13].

Chemical compound and disease context of Htr2a


Biological context of Htr2a

  • Sequencing demonstrated that the fragment overlapped the 5'-end of the 5-HT2 cDNA by 226 base pairs [18].
  • Screening of a rat genomic library was accomplished using 5'-directed fragments of 5-HT2 cDNA, and a 5.2-kilobase fragment was isolated [18].
  • These findings suggest that DOI-induced suppression of food intake is mediated by stimulation of both 5-HT1C and 5-HT2 receptors [19].
  • From these data we conclude that structurally distinct ligands can differentially regulate 5-HT 2A receptor signal transduction [20].
  • These antagonists yielded IC50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT2 receptor-mediated response [21].

Anatomical context of Htr2a

  • Previous studies from this laboratory have demonstrated that the 5-hydroxytryptamine (5-HT2) receptor subtype is transcriptionally regulated by 5-HT (serotonin) itself in rat myometrial smooth muscle cells [18].
  • Primer extension and RNase protection analyses indicated that three transcriptional start sites, which are common to both rat brain and myometrium, appear to exist and that the 5'-untranslated region of the 5-HT2 receptor cDNA is 1120 base pairs long [18].
  • 4. Pretreatment of ganglia with the 5-HT2 receptor agonist R-(+)-dimethoxy-4-iodoamphetamine (R-(+)-DOI, 1 microM) enhanced the tetanus-induced LTP [22].
  • 8. In conclusion, the tachykinin-induced contraction of the F334 rat isolated trachea is mediated by the stimulation of 5-HT2 receptors [23].
  • From these results, we propose that the 5-HT 2A receptor in the hyperalgesic hind paw function as an agonist-independent active receptor following constriction of the sciatic nerve, and that sarpogrelate and ketanserin act as inverse agonists of this receptor and suppress its activation [2].

Associations of Htr2a with chemical compounds


Physical interactions of Htr2a

  • Ketanserin (1) is a fairly selective 5-HT2 antagonist that binds both at 5-HT2A and 5-HT2C receptors [26].
  • Under such conditions, cortical 5-HT2 receptor binding sites as well as striatal 5-HT3 and dopamine-related binding sites remained unaltered [27].
  • Repeated treatment with ECS produced an increase in the density of 5-HT1A and tended to increase the specific binding of 5-HT2 serotonin receptors [28].
  • Strong activation of PLC via 5-HT2 receptors does however contribute to the synergy observed between 5-HT (Gi-coupled pathway) and fibroblast growth factor (tyrosine kinase-activated pathway) on DNA synthesis reinitiation in transfected cells [29].
  • We also found that in the presence of Mg2+ these metabotropic receptors resemble the NMDA receptor-ion channel complex interacted with 5-hydroxytryptamine2 (5-HT2) receptor signaling [30].

Regulatory relationships of Htr2a

  • Selective heterologous regulation of 5-HT1A receptor-stimulated 35S GTPgammaS binding in the anterior cingulate cortex as a result of 5-HT2 receptor activation [31].
  • Thus, while mRNA and possibly protein for multiple 5-HT receptors are present in aortic smooth muscle, only the 5-HT 2A receptor plays a significant role in directly modulating contractility and activating the Erk MAPK pathway [32].
  • 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 [33].
  • In addition, whereas chronic treatment with the strong D2 receptor-blocker haloperidol significantly downregulated hippocampal BDNF mRNA, the selective 5-HT2 receptor-blocker ritanserin significantly upregulated CA1 hippocampal BDNF mRNA in comparison to controls [34].
  • These responses included hyperglycemia, corticosterone release, and head shakes; cortical 5-HT2 receptor number and DOI-induced prolactin release (a 5-HT1C/5-HT2 receptor-mediated event) were also analyzed [35].

Other interactions of Htr2a

  • 5-HT1A, 5-HT2, and GABAB receptors interact to modulate neurotransmitter release probability in layer 2/3 somatosensory rat cortex as evaluated by the paired pulse protocol [36].
  • Conversely, neither 5-HT1, 5-HT2 nor 5-HT3 receptors played a role in the hyperglycaemic response to 2-DG [37].
  • These results suggest that 5-HT2 receptors have potential significance in brain development, with a functional difference between 5-HT2A and 5-HT2C receptor subtypes [38].
  • They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7 [39].
  • Therefore, the suppressive effect of these two 5-HT drugs on total and Polycose intake appears to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5-HT2 receptors (DOI) [40].

Analytical, diagnostic and therapeutic context of Htr2a

  • Here, we investigated the expression patterns of these 5-HT2 receptors in the rat brain during postnatal development by using Western blot and immunohistochemical analyses [38].
  • These effects could be prevented by prior local microinjection of a 5-HT2 receptor antagonist, ketanserin (10 pmol) [41].
  • Northern blot analysis demonstrated the presence of 5-HT2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT1A and 5-HT1C receptors were not detectable [21].
  • Moreover, RT-PCR indicated that 5-HT2 receptor mRNA is present in freshly isolated uterine tissue as well [21].
  • The different 5-HT2 agents used were applied intrastriatally at a 1 microM concentration through the microdialysis probe [42].


  1. 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]
  2. Contribution of the peripheral 5-HT 2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. Nitanda, A., Yasunami, N., Tokumo, K., Fujii, H., Hirai, T., Nishio, H. Neurochem. Int. (2005) [Pubmed]
  3. Comparative involvement of 5-HT1, 5-HT2 and 5-HT3 receptors in stress-induced colonic motor alterations in rats. Gué, M., Alary, C., Rio-Lacheze, C.D., Junien, J.L., Buéno, L. Eur. J. Pharmacol. (1993) [Pubmed]
  4. Signal transduction pathways responsible for serotonin-mediated prostaglandin G/H synthase expression in rat mesangial cells. Stroebel, M., Goppelt-Struebe, M. J. Biol. Chem. (1994) [Pubmed]
  5. 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]
  6. Cross-tolerance studies of serotonin receptors involved in behavioral effects of LSD in rats. Krebs, K.M., Geyer, M.A. Psychopharmacology (Berl.) (1994) [Pubmed]
  7. Activation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task. Koskinen, T., Ruotsalainen, S., Puumala, T., Lappalainen, R., Koivisto, E., Männistö, P.T., Sirviö, J. Neuropharmacology (2000) [Pubmed]
  8. Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. Rinaldi-Carmona, M., Congy, C., Santucci, V., Simiand, J., Gautret, B., Neliat, G., Labeeuw, B., Le Fur, G., Soubrie, P., Breliere, J.C. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  9. Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Gozlan, H., El Mestikawy, S., Pichat, L., Glowinski, J., Hamon, M. Nature (1983) [Pubmed]
  10. Serotonin regulates rhythmic whisking. Hattox, A., Li, Y., Keller, A. Neuron (2003) [Pubmed]
  11. 5-HT2 and 5-HT3 receptor subtypes mediate cholera toxin-induced intestinal fluid secretion in the rat. Beubler, E., Horina, G. Gastroenterology (1990) [Pubmed]
  12. Ketanserin: a selective antagonist of 5-HT2 serotoninergic receptors. Van Nueten, J.M., Leysen, J.E., Schuurkes, J.A., Vanhoutte, P.M. Lancet (1983) [Pubmed]
  13. Cloning and functional characterization of the rat stomach fundus serotonin receptor. Foguet, M., Hoyer, D., Pardo, L.A., Parekh, A., Kluxen, F.W., Kalkman, H.O., Stühmer, W., Lübbert, H. EMBO J. (1992) [Pubmed]
  14. Evidence that 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane-induced hypophagia and hyperthermia in rats is mediated by serotonin-2A receptors. Aulakh, C.S., Mazzola-Pomietto, P., Wozniak, K.M., Hill, J.L., Murphy, D.L. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  15. Evidence that 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in rats is mediated by stimulation of 5-HT2A receptors. Mazzola-Pomietto, P., Aulakh, C.S., Wozniak, K.M., Hill, J.L., Murphy, D.L. Psychopharmacology (Berl.) (1995) [Pubmed]
  16. Evidence for the involvement of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat. Ahlenius, S., Larsson, K., Fernandez-Guasti, A. Psychopharmacology (Berl.) (1989) [Pubmed]
  17. Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. Nash, J.F., Meltzer, H.Y., Gudelsky, G.A. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  18. Isolation and characterization of the rat 5-hydroxytryptamine type 2 receptor promoter: constitutive and inducible activity in myometrial smooth muscle cells. Du, Y.L., Wilcox, B.D., Teitler, M., Jeffrey, J.J. Mol. Pharmacol. (1994) [Pubmed]
  19. Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake suppressant effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Aulakh, C.S., Hill, J.L., Yoney, H.T., Murphy, D.L. Psychopharmacology (Berl.) (1992) [Pubmed]
  20. Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. Kurrasch-Orbaugh, D.M., Watts, V.J., Barker, E.L., Nichols, D.E. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  21. Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor. Rydelek-Fitzgerald, L., Wilcox, B.D., Teitler, M., Jeffrey, J.J. Mol. Cell. Endocrinol. (1993) [Pubmed]
  22. Induction and maintenance of ganglionic long-term potentiation require activation of 5-hydroxytryptamine (5-HT3) receptors. Alkadhi, K.A., Salgado-Commissariat, D., Hogan, Y.H., Akpaudo, S.B. J. Physiol. (Lond.) (1996) [Pubmed]
  23. Modulation by 5-HT1A receptors of the 5-HT2 receptor-mediated tachykinin-induced contraction of the rat trachea in vitro. Germonpré, P.R., Joos, G.F., Pauwels, R.A. Br. J. Pharmacol. (1998) [Pubmed]
  24. Functional study of rat 5-HT2A receptors using antisense oligonucleotides. Van Oekelen, D., Megens, A., Meert, T., Luyten, W.H., Leysen, J.E. J. Neurochem. (2003) [Pubmed]
  25. Transient and long-lasting actions of 5-HT on rat dentate gyrus neurones in vitro. Piguet, P., Galvan, M. J. Physiol. (Lond.) (1994) [Pubmed]
  26. Ketanserin analogues: the effect of structural modification on 5-HT2 serotonin receptor binding. Ismaiel, A.M., Arruda, K., Teitler, M., Glennon, R.A. J. Med. Chem. (1995) [Pubmed]
  27. 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]
  28. Effect of repeated treatment with electroconvulsive shock (ECS) on serotonin receptor density and turnover in the rat cerebral cortex. Nowak, G., Dulinski, J. Pharmacol. Biochem. Behav. (1991) [Pubmed]
  29. Cloning, functional expression and role in cell growth regulation of a hamster 5-HT2 receptor subtype. Van Obberghen-Schilling, E., Vouret-Craviari, V., Haslam, R.J., Chambard, J.C., Pouysségur, J. Mol. Endocrinol. (1991) [Pubmed]
  30. Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin2 receptor-stimulated signal transduction. Shinno, H., Mikuni, M., Saitoh, K., Tomita, U., Yamawaki, S., Takahashi, K. J. Neurochem. (1994) [Pubmed]
  31. Selective heterologous regulation of 5-HT1A receptor-stimulated 35S GTPgammaS binding in the anterior cingulate cortex as a result of 5-HT2 receptor activation. Valdez, M., Burke, T.F., Hensler, J.G. Brain Res. (2002) [Pubmed]
  32. Activation of Erk mitogen-activated protein kinase proteins by vascular serotonin receptors. Watts, S.W., Yang, P., Banes, A.K., Baez, M. J. Cardiovasc. Pharmacol. (2001) [Pubmed]
  33. 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]
  34. Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration. Chlan-Fourney, J., Ashe, P., Nylen, K., Juorio, A.V., Li, X.M. Brain Res. (2002) [Pubmed]
  35. Subchronic treatment with anxiolytic doses of the 5-HT1A receptor agonist ipsapirone does not affect 5-HT2 receptor sensitivity in the rat. Baudrie, V., De Vry, J., Broqua, P., Schmidt, B., Chaouloff, F., Glaser, T. Eur. J. Pharmacol. (1993) [Pubmed]
  36. 5-HT1A, 5-HT2, and GABAB receptors interact to modulate neurotransmitter release probability in layer 2/3 somatosensory rat cortex as evaluated by the paired pulse protocol. Torres-Escalante, J.L., Barral, J.A., Ibarra-Villa, M.D., Pérez-Burgos, A., Góngora-Alfaro, J.L., Pineda, J.C. J. Neurosci. Res. (2004) [Pubmed]
  37. 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]
  38. Unique expression patterns of 5-HT2A and 5-HT2C receptors in the rat brain during postnatal development: Western blot and immunohistochemical analyses. Li, Q.H., Nakadate, K., Tanaka-Nakadate, S., Nakatsuka, D., Cui, Y., Watanabe, Y. J. Comp. Neurol. (2004) [Pubmed]
  39. Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat. Lacau-Mengido, I.M., Libertun, C., Becú-Villalobos, D. Neuroendocrinology (1996) [Pubmed]
  40. 5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d-fenfluramine and DOI. Lawton, C.L., Blundell, J.E. Pharmacol. Biochem. Behav. (1993) [Pubmed]
  41. 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]
  42. Role of striatal serotonin2A and serotonin2C receptor subtypes in the control of in vivo dopamine outflow in the rat striatum. Lucas, G., Spampinato, U. J. Neurochem. (2000) [Pubmed]
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