Serotonergic signalling in the stomach and duodenum of patients with gastroparesis.
Serotonin (5-HT) is involved in the regulation of motoric and sensory functions of the upper gastrointestinal tract. The aim of the current study was to determine whether serotonergic signalling is altered in patients with idiopathic gastroparesis. Mucosal biopsy specimens were collected from the duodenum, antrum and fundus of 11 patients with idiopathic gastroparesis and 11 healthy controls. Neuroendocrine cells, specifically 5-HT producing cells, were counted after immunohistochemistry, and non-neuronal mRNA expression levels of tryptophan hydroxylase (TPH)-1, 5-HT transport protein (SERT), 5-HT3 and 5-HT4 receptor were quantified by real time RT-PCR. The number of 5-HT producing cells was comparable between patients and controls. No difference in expression of TPH-1 (rate limiting enzyme in 5-HT biosynthetic pathway) and SERT (responsible for 5-HT uptake) was found between patients and controls (P > 0.05). In the duodenum, the expression of the 5-HT3 receptor subunits and the 5-HT4 receptor was comparable between both groups. However, the 5-HT4(c) splice variant was expressed more abundantly in healthy controls compared to patients (P = 0.015). This study suggests that the delayed gastric emptying and upper abdominal symptoms in idiopathic gastroparesis do not result from altered mucosal 5-HT biosynthetic and uptake capacity.
van Lelyveld
N
N
Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands. n.van.lelyveld@meandermc.nl
Ter Linde
J
J
Schipper
M
M
Samsom
M
M
D000328:Adult; D004386:Duodenum / Q000502:physiology*; D005260:Female; D018589:Gastroparesis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D044406:Receptors, Serotonin, 5-HT3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000502:physiology*
D044406:Receptors, Serotonin, 5-HT3; D050486:Serotonin Plasma Membrane Transport Proteins; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin