Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine: involvement of H3 receptors.

Strips of the porcine small intestine were incubated in vitro, and the release of 5-hydroxytryptamine (5-HT) was determined by high-pressure liquid chromatography with electrochemical detection. Removal of the mucosa resulted in a large reduction (95%) of tissue 5-HT, suggesting that enterochromaffin cells are the main source of 5-HT. The release of 5-HT was reduced by 70% after omission of calcium. Tetrodotoxin and hexamethonium reduced the release of 5-HT by 30%-40% in a nonadditive manner, indicating a spontaneous neuronal (nicotinic) excitatory input to the enterochromaffin cells. Histamine inhibited the release of 5-HT by about 50%. This effect was not affected by mepyramine or cimetidine but was effectively blocked by thioperamide, indicating the involvement of H3 receptors. The selective H3-receptor agonist R-alpha-methyl-histamine also inhibited 5-HT release. Because the effect of R-alpha-methyl-histamine was also observed in the presence of tetrodotoxin, an indirect, neuronally mediated action could be excluded. Therefore, the inhibitory H3 receptors may be localized directly at the enterochromaffin cells.