5-HT-Actions in the Human Submucous Plexus

Serotonin (5-HT) plays a key role in the mammal organism being a multifunctional signalling molecule. In the gut, it is involved in the secretion of water and electrolytes and also in gastrointestinal motility regulation. It acts on enterocytes, directly on muscle cells and also via enteric neurons. The serotonin receptors involved are differently expressed between species and also between different regions of the gut. For example, 5-HT4-receptors have been found on cholinergic and tachykinergic neurons, whose activation causes contraction (1). In smooth muscles on the other hand they play a role in relaxation processes (2).

On enteric neurons the existence 5-HT3, 5-HT4 and to a lesser extent also 5-HT1P and 5-HT2- receptors has been shown. (3,4,5). Nevertheless, the involvement of serotonin receptors in the ENS needs further characterisation, not only to improve the understanding of the serotonin signalling processes in the intestines but also in context with functional bowel disorders like diarrhoeic diseases, nausea or IBS.
This also applies to the human submucous plexus, where the action of the 5-HT3-receptor has been verified by Michel et al (2005), further suggesting the involvement of 5-HT4R, 5-HT7R and 5-HT1PR in the ENS serotonin signalling(6).

Our actual studies on Serotonin aim to investigate the action of these receptors in the human submucous plexus by using fast imagining techniques together with the fluorescent voltage sensitive dye Di-8-ANEPPS (1-(3-sulfonatopropyl)-4-[_[2-(di-n-octylamino)-6-naphthyl]vinyl]pyridinium betaine) monitoring neuronal activity on a single cell level. As material serve human bowel tissue samples from patients undergoing surgery at the Medical Clinic of the Technische Universität München and the Medical Clinic Freising. After the preparation of the submucous plexus, the tissue is mounted on an epiflourescence microscope. Serotonin (1mM) is applied via local pressure microinjection directly onto the ganglion. Neuronal viability was tested by electrical stimulation of interganglionic fiber tracts.

Literature:
1. Briejer MR, Schuurkes JAJ; 1996, Eur J Pharmacol 308:173-180
2. Gershon, MD; 1999, Aliment Pharmacol Ther Suppl 2:15-30
3. Prins NH; 2001, Diss. Univ. Utrecht.
4. Spiller, RC; 2001, Curr Opin Gastroenterol 17:99-103
5. Talley, NJ; 2001, Lancet 358:2061-2068
6. Michel K et al 2005 Gastroenterol 128:1317–1326