A nonneuronal 5-hydroxytryptamine receptor 3 induces chloride secretion in the rat distal colonic mucosa.
BACKGROUND
The 5-HT3 receptor is a serotonin receptor believed to reside on enteric neurons. However, several studies belie an exclusive neural localization. Our hypothesis is that the 5-HT3 receptor agonist, 2-methyl-5-HT (2Me5HT), induces chloride secretion despite neural blockade, which can be blocked by a 5-HT3 receptor antagonist.


METHODS
Rat distal colon was stripped of its muscularis, mounted as mucosal sheets in Ussing chambers, and short-circuited. Adjacent sheets were pretreated with 1 micromol/L of the neurotoxin, tetrodotoxin, and incubated with 2Me5HT (50 micromol/L) alone or with a 5-HT3 (0.3 micromol/L ondansetron or 0.3 micromol/L tropisetron) or a 5-HT4 (0.3 micromol/L GR11808) receptor antagonist. Short-circuit current (I(sc)) was measured continuously.


RESULTS
2Me5HT caused an increase in I(sc), which was significantly (P <.01, repeated measures analysis of variance) inhibited by ondansetron (n = 8) and tropisetron (n = 5) but not by GR11808.


CONCLUSIONS
A 5-HT3 receptor is present at the mucosal level that mediates chloride secretion by a nonneural pathway.
Day
Jarrod
J
Department of Surgery, Virginia Commonwealth Medical Center, West Hospital, 15th Floor, West Wing, 1200 Broad St., P.O. Box 980519, Richmond, VA 23298-0519, USA.
King
Brian
B
Haque
Sheikh M
SM
Kellum
John M
JM
D000704:Analysis of Variance; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017294:Ondansetron / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000077526:Tropisetron
D002712:Chlorides; D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D012701:Serotonin; D013779:Tetrodotoxin; D017294:Ondansetron; D000077526:Tropisetron; C045918:2-methyl-5-HT