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 μmol/L of the neurotoxin, tetrodotoxin, and incubated with 2Me5HT (50 μmol/L) alone or with a 5-HT3 (0.3 μmol/L ondansetron or 0.3 μmol/L tropisetron) or a 5-HT4 (0.3 μmol/L GR11808) receptor antagonist. Short-circuit current (Isc) was measured continuously. Results 2Me5HT caused an increase in Isc, 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.