A 5-HT3 receptor agonist induces a chloride secretory response in the presence of neural blockade in rat distal colon

Abstract

Abstract Introduction: Serotonin (5-HT) is a well-described intestinal secretagogue. The 5-HT3 receptor is one of many 5-HT subtypes and is generally accepted to reside at the level of the enteric neuron. We hypothesize that a further subtype of the 5-HT3 receptor may be found on a nonneural cell in rat colon. Methods: Partial-thickness sheets of rat distal colon (n = 9) were mounted in Ussing chambers and short-circuited. The selective 5-HT3 receptor agonist, 2-met-5-HT (50 micromol), was added in the presence or absence of 1 micromol of the neural sodium channel blocker, tetrodotoxin (TTX). Control tissue received no drug. Changes in short-circuit current (Isc), a measure of electrogenic chloride secretion, was measured continuously. Results: Histologic examination of the stripped colon revealed intact mucosa and muscularis mucosa, scant submucosa, and virtually no neural ganglia (HE ANOVA) or TTX alone (p Conclusions: In this in vitro preparation of rat colon, the selective 5-HT3 receptor agonist, 2-met-5-HT, induced a chloride secretory response that was TTX-insensitive. These findings suggest the presence of a nonneural 5-HT3 receptor located at the level of the mucosa. TableMean (+/− SEM) changes in Isc from baseline in microamps/cm 2 MinControl2Met5HT∗2Met5HT + TTX∗TTX5−1.3 ± 0.911.3 ± 2.28.1 ± 3.0−0.3 ± 0.210−1.8 ± 1.912.0 ± 3.37.3 ± 1.9−0.8 ± 0.315−3.3 ± 3.09.3 ± 1.86.7 ± 1.6−0.8 ± 0.430−4.3 ± 4.18.6 ± 1.95.2 ± 1.2−0.9 ± 0.660−5.0 ± 4.35.5 ± 2.12.0 ± 0.8−1.1 ± 0.7∗p