The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HTR4  -  5-hydroxytryptamine (serotonin) receptor 4...

Homo sapiens

Synonyms: 5-HT-4, 5-HT4, 5-HT4R, 5-hydroxytryptamine receptor 4, Serotonin receptor 4
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HTR4


Psychiatry related information on HTR4


High impact information on HTR4

  • These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin [8].
  • The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known [9].
  • Serotonin inhibits Na+/H+ exchange activity via 5-HT4 receptors and activation of PKC alpha in human intestinal epithelial cells [10].
  • Studies using specific inhibitors and agonists showed that the effects of 5-HT were mediated by 5-HT4 receptors [10].
  • The effects of the 5-HT3 and 5-HT4 antagonists in guinea pig colon were additive [11].

Chemical compound and disease context of HTR4


Biological context of HTR4


Anatomical context of HTR4


Associations of HTR4 with chemical compounds

  • Neither uncoupling nor beta-arrestin/dynamin-dependent endocytosis required the serine and threonine residues localized within the specific C-terminal domains of the 5-HT4R splice variants [21].
  • Taken together, our results show an overexpression of the 5-HT4 receptor in cisapride-responsive AIMAH [1].
  • In these tissues, 5-HT4 receptor mRNA expression was 3 to 16 times higher than in normal glands, likely explaining the abnormal in vivo cortisol response to cisapride [1].
  • Moreover, we further identified a sequence within the C-terminal tail upstream of L358, rich in serine and threonine residues, that played a crucial role in maintaining 5-HT4R under its inactive conformation [22].
  • Hypomotility remains an attractive therapeutic target in IBS and the new generation of prokinetics includes several partial agonists at the 5-HT4 receptor, such as tegaserod (HTF-919) and prucalopride (R0-93877) [23].

Regulatory relationships of HTR4


Other interactions of HTR4

  • The T allele of the 83097 C>T polymorphism of HTR4 showed a tendency of preferential transmission to probands with ADHD (chi(2)=2.699, P=0.100) [17].
  • The preferential 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (up to 0.3 microM) and the selective 5-HT4 receptor agonist cisapride (up to 1 microM) failed to inhibit tritium overflow [25].
  • Serotonin receptors belonging to the 5-HT3 and 5-HT4 subtype are the most extensively studied in gastroenterology, although hitherto 'orphan' receptor subtypes, such as the 5-HT7 and the 5-HT(1B/D) receptors, are now emerging [23].
  • Both PHA stimulated human and monkey PBMCs express mRNAs for 5-HT1(A), 5-HT1(B), 5-HT1(E), 5-HT2(A), 5-HT3, 5-HT4, 5-HT6 receptor types/subtypes [26].
  • Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin [27].

Analytical, diagnostic and therapeutic context of HTR4


  1. Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome. Cartier, D., Lihrmann, I., Parmentier, F., Bastard, C., Bertherat, J., Caron, P., Kuhn, J.M., Lacroix, A., Tabarin, A., Young, J., Vaudry, H., Lefebvre, H. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  2. Expression profile of serotonin4 (5-HT4) receptors in adrenocortical aldosterone-producing adenomas. Cartier, D., Jégou, S., Parmentier, F., Lihrmann, I., Louiset, E., Kuhn, J.M., Bastard, C., Plouin, P.F., Godin, M., Vaudry, H., Lefebvre, H. Eur. J. Endocrinol. (2005) [Pubmed]
  3. Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells. Contesse, V., Lefebvre, H., Lenglet, S., Kuhn, J.M., Delarue, C., Vaudry, H. Can. J. Physiol. Pharmacol. (2000) [Pubmed]
  4. 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Manzke, T., Guenther, U., Ponimaskin, E.G., Haller, M., Dutschmann, M., Schwarzacher, S., Richter, D.W. Science (2003) [Pubmed]
  5. Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees. Ohtsuki, T., Ishiguro, H., Detera-Wadleigh, S.D., Toyota, T., Shimizu, H., Yamada, K., Yoshitsugu, K., Hattori, E., Yoshikawa, T., Arinami, T. Mol. Psychiatry (2002) [Pubmed]
  6. Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac. Robert, S., Maillet, M., Morel, E., Launay, J.M., Fischmeister, R., Mercken, L., Lezoualc'h, F. FEBS Lett. (2005) [Pubmed]
  7. Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility. Taniyama, K., Makimoto, N., Furuichi, A., Sakurai-Yamashita, Y., Nagase, Y., Kaibara, M., Kanematsu, T. J. Gastroenterol. (2000) [Pubmed]
  8. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. Lacroix, A., Ndiaye, N., Tremblay, J., Hamet, P. Endocr. Rev. (2001) [Pubmed]
  9. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Hoyer, D., Clarke, D.E., Fozard, J.R., Hartig, P.R., Martin, G.R., Mylecharane, E.J., Saxena, P.R., Humphrey, P.P. Pharmacol. Rev. (1994) [Pubmed]
  10. Serotonin inhibits Na+/H+ exchange activity via 5-HT4 receptors and activation of PKC alpha in human intestinal epithelial cells. Gill, R.K., Saksena, S., Tyagi, S., Alrefai, W.A., Malakooti, J., Sarwar, Z., Turner, J.R., Ramaswamy, K., Dudeja, P.K. Gastroenterology (2005) [Pubmed]
  11. Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine. Foxx-Orenstein, A.E., Kuemmerle, J.F., Grider, J.R. Gastroenterology (1996) [Pubmed]
  12. The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression. Lötsch, J., Skarke, C., Schneider, A., Hummel, T., Geisslinger, G. Clin. Pharmacol. Ther. (2005) [Pubmed]
  13. Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome. Bourdeau, I., D'Amour, P., Hamet, P., Boutin, J.M., Lacroix, A. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  14. Modulation of intestinal gas dynamics in healthy human volunteers by the 5-HT receptor agonist tegaserod. Coleski, R., Owyang, C., Hasler, W.L. Am. J. Gastroenterol. (2006) [Pubmed]
  15. The pharmacokinetics of the novel promotile drug, tegaserod, are similar in healthy subjects-male and female, elderly and young. Appel-Dingemanse, S., Horowitz, A., Campestrini, J., Osborne, S., McLeod, J. Aliment. Pharmacol. Ther. (2001) [Pubmed]
  16. Assignment of the human serotonin 4 receptor gene (HTR4) to the long arm of chromosome 5 (5q31-q33). Cichon, S., Kesper, K., Propping, P., Nöthen, M.M. Mol. Membr. Biol. (1998) [Pubmed]
  17. Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects. Li, J., Wang, Y., Zhou, R., Wang, B., Zhang, H., Yang, L., Faraone, S.V. Neurosci. Lett. (2006) [Pubmed]
  18. Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines. Dizeyi, N., Bjartell, A., Hedlund, P., Taskén, K.A., Gadaleanu, V., Abrahamsson, P.A. Eur. Urol. (2005) [Pubmed]
  19. Serotonin receptor subtype mRNA expression in human ocular tissues, determined by RT-PCR. Sharif, N.A., Senchyna, M. Mol. Vis. (2006) [Pubmed]
  20. Cloning and expression of a human serotonin 5-HT4 receptor cDNA. Van den Wyngaert, I., Gommeren, W., Verhasselt, P., Jurzak, M., Leysen, J., Luyten, W., Bender, E. J. Neurochem. (1997) [Pubmed]
  21. Uncoupling and endocytosis of 5-hydroxytryptamine 4 receptors. Distinct molecular events with different GRK2 requirements. Barthet, G., Gaven, F., Framery, B., Shinjo, K., Nakamura, T., Claeysen, S., Bockaert, J., Dumuis, A. J. Biol. Chem. (2005) [Pubmed]
  22. Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. Claeysen, S., Sebben, M., Becamel, C., Bockaert, J., Dumuis, A. Mol. Pharmacol. (1999) [Pubmed]
  23. Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. De Ponti, F., Tonini, M. Drugs (2001) [Pubmed]
  24. The role of 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors in the regulation of gut motility in the ferret. Nagakura, Y., Kiso, T., Ito, H., Miyata, K., Yamaguchi, T. Life Sci. (2000) [Pubmed]
  25. Inhibition of noradrenaline release via presynaptic 5-HT1D alpha receptors in human atrium. Molderings, G.J., Frölich, D., Likungu, J., Göthert, M. Naunyn Schmiedebergs Arch. Pharmacol. (1996) [Pubmed]
  26. Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the peripheral blood mononuclear cells of rhesus macaques. Yang, G.B., Qiu, C.L., Zhao, H., Liu, Q., Shao, Y. J. Neuroimmunol. (2006) [Pubmed]
  27. Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin. López-Rodríguez, M.L., Murcia, M., Benhamú, B., Olivella, M., Campillo, M., Pardo, L. J. Comput. Aided Mol. Des. (2001) [Pubmed]
  28. Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31-->q33 by in situ hybridization. Claeysen, S., Faye, P., Sebben, M., Lemaire, S., Bockaert, J., Dumuis, A., Taviaux, S. Cytogenet. Cell Genet. (1997) [Pubmed]
  29. Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. Suzuki, T., Iwata, N., Kitamura, Y., Kitajima, T., Yamanouchi, Y., Ikeda, M., Nishiyama, T., Kamatani, N., Ozaki, N. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
WikiGenes - Universities