Expression of 5-HT3 receptors in the rat gastrointestinal tract.
OBJECTIVE
Functional effects mediated via the 5-hydroxytryptamine3 receptor (5-HT3R) can be elicited from both extrinsic and intrinsic neurons innervating the gastrointestinal (GI) tract. Clinically, 5-HT3 antagonists are important in the treatment of emesis and have been used for the treatment of symptoms in functional bowel disease. The aim of the present study was to elucidate the cellular sites of 5-HT3R expression in the rat GI tract using immunohistochemistry.


METHODS
Immunohistochemistry was performed in fixed cryostat sections and whole mounts of stomach and intestine of fasted rats, using an affinity-purified antibody directed to a 19-amino acid sequence of the cytoplasmic loop of the 5-HT3R.


RESULTS
5-HT3R immunoreactivity was localized to numerous neurons of the myenteric and submucosal plexus, concentrated primarily near the neuronal plasma membrane, and to fibers in the circular and longitudinal muscles, submucosa, and mucosa. 5-HT3R immunoreactivity was also expressed by interstitial cells of Cajal and a few endocrine cells. Numerous 5-HT3R-positive myenteric neurons were cholinergic, and few neurons coexpressed VIP or SP immunoreactivity. Fibers immunoreactive for 5-HT3R in the duodenal but not ileal mucosa were markedly reduced by subdiaphragmatic vagotomy or chemical denervation of vagal afferents.


CONCLUSIONS
These findings indicate that 5-HT3Rs are expressed by distinct cells in the GI tract, including functionally distinct classes of neurons, interstitial cells of Cajal, and endocrine cells. The effects of serotonin mediated by 5-HT3Rs involve the activation of neuronal and nonneuronal pathways.
Glatzle
Jörg
J
Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California 95616, USA.
Sternini
Catia
C
Robin
Carla
C
Zittel
Tilman T
TT
Wong
Helen
H
Reeve
Joseph R
JR
Raybould
Helen E
HE
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003714:Denervation; D004064:Digestive System / Q000294:innervation / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D013368:Submucous Plexus / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D002211:Capsaicin