Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples

Background The serotonin type 4 (5-HT(4)) 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-HT(4) 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-HT(4) receptor messenger RNA expression in the gut. Method 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-HT(4) 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-HT(4) 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-HT(4) receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT(4) receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.