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.
Schwörer
H
H
Department of Medicine, University of Göttingen, Germany.
Katsoulis
S
S
Racké
K
K
D000818:Animals; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013552:Swine
D008761:Methylhistamines; D011968:Receptors, Histamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C069357:alpha-methylhistamine; D006632:Histamine; D011738:Pyrilamine