Centrally administered thyrotropin-releasing hormone (TRH) stimulates colonic transit and diarrhea production by a vagally mediated serotonergic mechanism in the rabbit.

The effect of centrally administered thyrotropin-releasing hormone (TRH) (1, 10 or 100 micrograms) on transit of a charcoal marker placed in the proximal colon of anesthetized rabbits was determined. A dose-dependent stimulation of transit was produced, which, with the higher doses, was accompanied by a watery diarrhea. Pretreatment with atropine was ineffective against these effects. Hexamethonium or bilateral vagotomy attenuated these effects, whereas vagotomy + sacral cord transection completely abolished them. Several serotonin antagonists completely blocked, and fluoxetine markedly enhanced, the TRH-induced transit and diarrhea production. Measurement of portal blood demonstrated that TRH produced a dose-dependent elevation in serotonin levels. This response was blocked by pretreatment with hexamethonium or after bilateral vagotomy, but enhanced by fluoxetine. These observations indicate that centrally administered TRH activates colonic transit via a vagally mediated serotonergic mechanism. The release of serotonin is probably from the enterochromaffin cells and/or enteric serotonin neurons in the intestine.