DIFFERENTIAL 5-HT3 MEDIATION OF HUMAN GASTROCOLONIC RESPONSE AND COLONIC PERISTALTIC REFLEX

Colonic motor function is modulated by extended and local neural refle xes involving unknown mediators. To test the role of serotonin (5-HT3) pathways, increases in colonic tone during antral distension and duod enal lipid perfusion (gastrocolonic responses) and changes in orad and caudad colonic tone in response to local colonic distension (peristal tic reflex) were measured after double-blind granisetron (10 mu g/kg) or placebo infusion in healthy human volunteers. Antral distension evo ked increases in colonic tone, which were blunted by granisetron (P < 0.05) without effects on antral compliance. Intraduodenal lipid perfus ion also evoked increased colonic tone, which was reduced by granisetr on (P < 0.05). In contrast, orad colonic contractions and caudad relax ations and contractions during colonic distension were unaffected by g ranisetron. In conclusion, 5-HT3 receptor antagonism blunts both the m echano- and chemoreceptor components of the human gastrocolonic respon se without altering antral compliance. In contrast, 5-HT3 pathways pla y no role in the ascending or descending components of the colonic per istaltic reflex. These findings demonstrate different roles for 5-HT3 receptors in the control of colonic motor function by the proximal gas trointestinal tract and by local neural reflexes.