Stroking human jejunal mucosa induces 5-HT release and Cl- secretion via afferent neurons and 5-HT4 receptors

5-Hydroxytryptamine (5-HT) release and neural reflex pathways activated in response to mucosal stroking were investigated in muscle-stripped human jejunum mounted in modified Ussing chambers. The mucosa was stroked with a brush at 1/s for 1-10 s. Mucosal stroking resulted in a significant increase in the concentration of 5-HT in the mucosal bath within 5 min. It also was associated with a reproducible positive change (Delta) in short-circuit current (I-sc), which was abolished by inhibitors of chloride secretion. Capsaicin and hexamethonium significantly inhibited the Delta I-sc but not the release of 5-HT. The Delta I-sc was inhibited by TTX but not by atropine. It was also inhibited by the 5-HT3,4 receptor antagonist tropisetron (10 mu M) and the 5-HT4,3 receptor antagonist SDZ-205-557 (10 mu M) but not by preferential antagonists of 5-HT1P, 5-HT2A, Or 5-HT3 receptors. These results suggest that mucosal stroking induces release of mucosal 5-HT, which activates a 5-HT4 receptor on enteric sensory neurons, evoking a neuronal reflex that stimulates chloride secretion.