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 (Isc), which was abolished by inhibitors of chloride secretion. Capsaicin and hexamethonium significantly inhibited the DeltaIsc but not the release of 5-HT. The DeltaIsc was inhibited by TTX but not by atropine. It was also inhibited by the 5-HT(3,4) receptor antagonist tropisetron (10 microM) and the 5-HT(4,3) receptor antagonist SDZ-205-557 (10 microM) but not by preferential antagonists of 5-HT(1P), 5-HT(2A), 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.
Kellum
J M
JM
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0161, USA. jkellum@hsc.vcu.edu
Albuquerque
F C
FC
Stoner
M C
MC
Harris
R P
RP
D002211:Capsaicin / Q000494:pharmacology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004553:Electric Conductivity; D006801:Humans; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D007583:Jejunum / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D010812:Physical Stimulation; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D026941:Sodium Channel Blockers; D012701:Serotonin; D013779:Tetrodotoxin; D002211:Capsaicin