Serotonin receptor diversity in the human colon: expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E

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 functiona...

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Main Authors: Kapeller, Johannes (Author) , Möller, Dorothee (Author) , Lasitschka, Felix (Author) , Autschbach, Frank (Author) , Hovius, Ruud (Author) , Rappold, Gudrun (Author) , Brüss, Michael (Author) , Gershon, Michael D. (Author) , Niesler, Beate (Author)
Format: Article (Journal)
Language:English
Published: 2011
In: The journal of comparative neurology
Year: 2011, Volume: 519, Issue: 3, Pages: 420-432
ISSN:1096-9861
DOI:10.1002/cne.22525
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/cne.22525
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/cne.22525
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Author Notes:Johannes Kapeller, Dorothee Möller, Felix Lasitschka, Frank Autschbach, Ruud Hovius, Gudrun Rappold, Michael Brüss, Michael D. Gershon, and Beate Niesler

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520 |a 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. J. Comp. Neurol. 519:420-432, 2011. © 2010 Wiley-Liss, Inc. 
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