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

J Comp Neurol. 2011 Feb 15;519(3):420-32. doi: 10.1002/cne.22525.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Cell Line
  • Colon / anatomy & histology
  • Colon / metabolism*
  • Female
  • Humans
  • Male
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Serotonin / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • HTR3A protein, human
  • HTR3C protein, human
  • HTR3D protein, human
  • HTR3E protein, human
  • Microfilament Proteins
  • Protein Subunits
  • Receptors, Serotonin, 5-HT3
  • villin
  • Serotonin
  • Sodium-Potassium-Exchanging ATPase