Gastroenterology

Gastroenterology

Volume 128, Issue 5, May 2005, Pages 1317-1326
Gastroenterology

Basic-alimentary tract
Serotonin Excites Neurons in the Human Submucous Plexus via 5-HT3 Receptors

https://doi.org/10.1053/j.gastro.2005.02.005Get rights and content

Background & Aims: Serotonin (5-hydroxytryptamine [5-HT]) is a key signaling molecule in the gut. Recently, the neural 5-HT3 receptor received a lot of attention as a possible target in functional bowel diseases. Yet, the 5-HT3 receptor–mediated changes in properties of human enteric neurons is unknown. Methods: We used a fast imaging technique in combination with the potentiometric dye 1-(3-sulfonatopropyl)-4-[β[2-(di-n-octylamino)-6-naphthyl]vinyl]pyridinium betaine to monitor directly the membrane potential changes in neurons of human submucous plexus from surgical specimens of 21 patients. An Ussing chamber technique was used to study 5-HT3 receptor involvement in chloride secretion. Results: Local microejection of 5-HT directly onto ganglion cells resulted in a transient excitation of enteric neurons characterized by increased spike discharge. This response was mimicked by the 5-HT3 receptor agonist, 2-methyl-5-HT, and blocked by the 5-HT3 receptor antagonist, tropisetron. The proportions of 5-HT–responsive nerve cells per ganglion ranged from 25.5% ± 18.4% in the duodenum to 54.2% ± 46.9% in the colon. Interestingly, 2-methyl-5-HT did not evoke chloride secretion in the human intestine but it did in the guinea-pig intestine. Specific 5-HT3A and 5-HT3B receptor subunit immunoreactivity as well as 5-HT3A and 5-HT3B receptor–specific messenger RNA were detected in the tissue samples. Based on co-labeling with the pan-neuronal marker HuC/D we conclude that submucous nerve cells potentially express heteromeric 5-HT3A/B receptors. Conclusions: We show that 5-HT excited human enteric neurons via 5-HT3 receptors, which may comprise both 5-HT3A and 5-HT3B receptor subunits.

Section snippets

Tissue Samples

Human tissue samples of small and large bowel were obtained from 28 patients undergoing surgery in the Departments of Surgery at the Medical Clinic in Freising and the Medical Clinic of the Technische Universität in München. Diagnoses that led to the surgery were as follows: carcinoma of the small or large bowel (19 patients), polyposis (1 patient), diverticulitis (3 patients), Crohn’s diseae (1 patient), ovarian cancer (2 patients), pancreatic carcinoma (1 patient), and ulcerative colitis (1

Neuroimaging

Experiments were performed on 24 preparations from 21 patients (10 men, 11 women; mean age: 62.3 ± 15.7 years; range, 31–89 years). A total of 50 ganglia containing 421 nerve cells were analyzed. The mean number of nerve cells per ganglion was 8.4 ± 6.1 (range, 1–40).

Application of 5-HT or the selective 5-HT3 receptor agonist 2-methyl-5-HT to ganglion cells in the submucous plexus resulted in an excitatory response in 33 of 50 ganglia (Figure 1). Only in 2 preparations from 2 patients (4

Discussion

With this study we showed the presence of functional 5-HT3 receptors that on activation excited neurons in the human submucous plexus. This conclusion is based on the finding that the 5-HT3 receptor agonist, 2-methyl-5-HT, mimicked the excitatory 5-HT response, and that a selective concentration of the 5-HT3 antagonist, tropisetron, antagonized the response to 5-HT. The tropisetron-insensitive component of the 5-HT response that was detected in a few enteric nerve cells suggests the involvement

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  • Cited by (0)

    Supported by DFG Sche 267/5-1, 5-2, and the Wellcome Trust.

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