J Neurogastroenterol Motil.  2015 Jul;21(3):361-369. 10.5056/jnm14157.

Distribution of 5-HT3, 5-HT4, and 5-HT7 Receptors Along the Human Colon

Affiliations
  • 1Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville Victoria, Australia. helen.irving@monash.edu
  • 2Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
  • 3School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.

Abstract

BACKGROUND/AIMS
Several disorders of the gastrointestinal tract are associated with abnormal serotonin (5-HT) signaling or metabolism where the 5-HT3 and 5-HT4 receptors are clinically relevant. The aim was to examine the distribution of 5-HT3, 5-HT4, and 5-HT7 receptors in the normal human colon and how this is associated with receptor interacting chaperone 3, G protein coupled receptor kinases, and protein LIN-7 homologs to extend previous observations limited to the sigmoid colon or the upper intestine.
METHODS
Samples from ascending, transverse, descending, and sigmoid human colon were dissected into 3 separate layers (mucosa, longitudinal, and circular muscles) and ileum samples were dissected into mucosa and muscle layers (n = 20). Complementary DNA was synthesized by reverse transcription from extracted RNA and expression was determined by quantitative or end point polymerase chain reaction.
RESULTS
The 5-HT3 receptor subunits were found in all tissues throughout the colon and ileum. The A subunit was detected in all samples and the C subunit was expressed at similar levels while the B subunit was expressed at lower levels and less frequently. The 5-HT3 receptor E subunit was mainly found in the mucosa layers. All splice variants of the 5-HT4 and 5-HT7 receptors were expressed throughout the colon although the 5-HT4 receptor d, g, and i variants were expressed less often.
CONCLUSIONS
The major differences in 5-HT receptor distribution within the human colon are in relation to the mucosa and muscular tissue layers where the 5-HT3 receptor E subunit is predominantly found in the mucosal layer which may be of therapeutic relevance.

Keyword

Colon; G protein coupled receptor kinases; Ileum; Receptors, serotonin

MeSH Terms

Colon*
Colon, Sigmoid
DNA, Complementary
G-Protein-Coupled Receptor Kinases
Gastrointestinal Tract
Humans
Ileum
Intestines
Metabolism
Mucous Membrane
Polymerase Chain Reaction
Receptors, Serotonin
Receptors, Serotonin, 5-HT3
Receptors, Serotonin, 5-HT4
Reverse Transcription
RNA
Serotonin
DNA, Complementary
G-Protein-Coupled Receptor Kinases
RNA
Receptors, Serotonin
Receptors, Serotonin, 5-HT3
Receptors, Serotonin, 5-HT4
Serotonin
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