Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors.
OBJECTIVE
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-[beta[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.
Michel
Klaus
K
Department of Human Biology, Technische Universität Munich, Freising, Germany.
Zeller
Florian
F
Langer
Rupert
R
Nekarda
Hjalmar
H
Kruger
Dagmar
D
Dover
Terri J
TJ
Brady
Catherine A
CA
Barnes
Nicholas M
NM
Schemann
Michael
M
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*; D013368:Submucous Plexus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D002712:Chlorides; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin