Regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) 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-HT(4) receptor and 5-HT(3) 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-HT(4) receptor and the 5-HT(3C) and 5-HT(3E) 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-HT(3) and 5-HT(4) 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.
van Lelyveld
N
N
Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands. n.vanlelyveld@azu.nl
Ter Linde
J
J
Schipper
M E I
ME
Samsom
M
M
D000328:Adult; D004386:Duodenum / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013270:Stomach / Q000033:anatomy & histology; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
D021122:Protein Subunits; D012333:RNA, Messenger; D044406:Receptors, Serotonin, 5-HT3; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044422:Receptors, Serotonin, 5-HT4; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase