Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples.
BACKGROUND
The serotonin type 4 (5-HT4) receptor has been associated with functions of the gastrointestinal tract such as modulation of the peristaltic reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been shown to accelerate gastric emptying and improve symptoms of constipation in animals and humans. However, detailed data on the expression profile and on the localization of this receptor subtype are lacking so far.


OBJECTIVE
To study the pattern and expression levels of 5-HT4 receptor messenger RNA expression in the gut.


METHODS
Normal tissue samples were collected from the whole gastrointestinal tract of patients undergoing abdominal surgery and, in addition, of monkeys. We performed a comprehensive analysis of 5-HT4 receptor expression by quantitative reverse transcription-polymerase chain reaction, using human and non-human primate tissues from the oesophagus to the rectum. In addition, the brain and heart of non-human primates were analysed.


RESULTS
Significantly higher levels of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum, ileum and caecum and also in the corresponding non-human primate gut segments, ranging from 2- to 12-fold compared with the liver. No differences were found between females and males of both human and non-human primates.


CONCLUSIONS
These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.
Mader
Robert
R
Novartis Institutes for BioMedical Research, GI Department, Basel, Switzerland.
Kocher
Thomas
T
Haier
Joerg
J
Wieczorek
Grazyna
G
Pfannkuche
Hans-Juergen
HJ
Ito
Moriko
M
D000818:Animals; D005260:Female; D041981:Gastrointestinal Tract / Q000737:chemistry*; D006801:Humans; D008297:Male; D011323:Primates; D012333:RNA, Messenger / Q000032:analysis; D044422:Receptors, Serotonin, 5-HT4 / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D012333:RNA, Messenger; D044422:Receptors, Serotonin, 5-HT4