Journal
JOURNAL OF COMPARATIVE NEUROLOGY
Volume 519, Issue 3, Pages 420-432Publisher
WILEY
DOI: 10.1002/cne.22525
Keywords
5-HT receptor; 5-HT3; ligand-gated ion channel; antibody; gastrointestinal tract
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Funding
- German Federal Ministry for Education and Research [BMBF0313320]
- National Genome Research Network (NGFN-2) [EP-S19T02]
- German Cancer Aid [107229]
- Human Frontier Science Program
- U.S. Public Health Service (NIH) [NS12969]
- Swiss National Science Foundation [31003A-109886]
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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. (C) 2010 Wiley-Liss, Inc.
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