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Am J Physiol Gastrointest Liver Physiol 277: G515-G520, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 3, G515-G520, September 1999

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

John M. Kellum, Francisco C. Albuquerque, Michael C. Stoner, and R. Paul Harris

Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0161

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 (Isc), which was abolished by inhibitors of chloride secretion. Capsaicin and hexamethonium significantly inhibited the Delta Isc but not the release of 5-HT. The Delta Isc was inhibited by TTX but not by atropine. It was also inhibited by the 5-HT3,4 receptor antagonist tropisetron (10 µM) and the 5-HT4,3 receptor antagonist SDZ-205-557 (10 µM) 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.

serotonin; serotonin receptors; enteric neurons; intestinal secretion; short-circuit current; chloride; capsaicin; 5-hydroxytryptamine


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