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Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5‐HT3C, 5‐HT3D, and 5‐HT3E
Author(s) -
Kapeller Johannes,
Möller Dorothee,
Lasitschka Felix,
Autschbach Frank,
Hovius Ruud,
Rappold Gudrun,
Brüss Michael,
Gershon Michael D.,
Niesler Beate
Publication year - 2010
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22525
Subject(s) - biology , receptor , myenteric plexus , immunocytochemistry , 5 ht receptor , protein subunit , serotonin , enteric nervous system , western blot , microbiology and biotechnology , gene isoform , immunohistochemistry , neuroscience , gene , endocrinology , genetics , immunology
Since the first description of 5‐HT 3 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‐HT 3 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‐HT 3 receptor subtypes play in the function of the enteric and central nervous systems and the contribution that specific 5‐HT 3 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.