title: Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E.
abstract: Since the first description of 5-HT₃ receptors more than 50 years ago, there has been speculation about the molecular basis of their receptor heterogeneity. We have cloned the genes encoding novel 5-HT3 subunits 5-HT3C, 5-HT3D, and 5-HT3E and have shown that these subunits are able to form functional heteromeric receptors when coexpressed with the 5-HT3A subunit. However, whether these subunits are actually expressed in human tissue remained to be confirmed. In the current study, we performed immunocytochemistry to locate the 5-HT3A as well as the 5-HT3C, 5-HT3D, and 5-HT3E subunits within the human colon. Western blot analysis was used to confirm subunit expression, and RT-PCR was employed to detect transcripts encoding 5-HT₃ receptor subunits in microdissected tissue samples. This investigation revealed, for the first time, that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons. Furthermore, 5-HT3A and 5-HT3D were found to be expressed in submucosal plexus of the human large intestine. These data provide a strong basis for future studies of the roles that specific 5-HT₃ receptor subtypes play in the function of the enteric and central nervous systems and the contribution that specific 5-HT₃ receptors make to the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome and dyspepsia.
authors.affiliation: Department of Human Molecular Genetics, University of Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kapeller
authors.forename: Dorothee
authors.initials: D
authors.lastname: Möller
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.forename: Frank
authors.initials: F
authors.lastname: Autschbach
authors.forename: Ruud
authors.initials: R
authors.lastname: Hovius
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
authors.forename: Michael
authors.initials: M
authors.lastname: Brüss
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gershon
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
mesh_terms: D000368:Aged; D002460:Cell Line; D003106:Colon / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: C509409:HTR3A protein, human; C543516:HTR3C protein, human; C476054:HTR3D protein, human; C476055:HTR3E protein, human; D008840:Microfilament Proteins; D021122:Protein Subunits; D044406:Receptors, Serotonin, 5-HT3; C026615:villin; D012701:Serotonin; D000254:Sodium-Potassium-Exchanging ATPase