CENTRALLY ADMINISTERED THYROTROPIN-RELEASING-HORMONE (TRH) STIMULATES COLONIC TRANSIT AND DIARRHEA PRODUCTION BY A VAGALLY MEDIATED SEROTONERGIC MECHANISM IN THE RABBIT

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Abstract
The effect of centrally administered TRH (1, 10 or 100 .mu.g) 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. Centrally administered TRH apparently 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.