Regional differences in expression of TPH-1, SERT, 5-HT3 and 5-HT4 receptors in the human stomach and duodenum

The aim of this study was to increase the understanding of the role of serotonergic signalling in normal gastroduodenal function at a molecular level. Mucosal biopsy specimens were collected from the fundus, antrum and duodenum of 11 healthy subjects. Serotonin (5-HT)-positive cells were counted and the mRNA levels of tryptophan hydroxylase (TPH), serotonin transporter (SERT), 5-HT4 receptor and 5-HT3 receptor subunits were quantified by real-time reverse transcription polymerase chain reaction. The number of 5-HT-positive cells was larger in the duodenum compared with the stomach (P < 0.001). Serotonin transport protein expression was 19-fold higher in the duodenum compared with the antrum and 457-fold higher compared with the fundus (P < 0.001). Tryptophan hydroxylase-1 expression was lower in the duodenum compared with the antrum and fundus (regional differences -2.3 and -3.6, respectively). The 5-HT4 receptor and the 5-HT3C and 5-HT3E receptor subunits were more abundantly expressed in duodenum compared with the stomach (P < 0.001). The larger number of 5-HT-positive cells, the higher expression of 5-HT3 and 5-HT4 receptors, and in particularly the higher uptake capacity of 5-HT in the duodenum, point out to a more prominent role of serotonergic signalling at the mucosal level in the duodenum compared with the stomach.