Spontaneous release of endogenous 5-hydroxytryptamine and 5-hydroxyindoleacetic acid from the isolated vascularly perfused ileum of the guinea-pig.
The spontaneous release of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid from the enterochromaffin cells of the small intestine into the portal circulation was investigated in vitro using the vascularly perfused ileum of the guinea-pig. The release of 5-hydroxytryptamine decreased by 70% in a calcium-free medium and by 35% in the presence of tetrodotoxin. Inhibition of monoamine oxidase activity by pargyline (100 microM) had no effect on the spontaneous release of 5-hydroxytryptamine although it caused a 75% reduction in the outflow of 5-hydroxyindoleacetic acid. Imipramine (1 microM), an inhibitor of neuronal uptake of 5-hydroxytryptamine, reduced the 5-hydroxyindoleacetic acid outflow by 57% and increased the release of 5-hydroxytryptamine by 66%. The combination of both drugs showed no additional effect. The tissue content of 5-hydroxytryptamine and its metabolite was not changed after perfusion with the precursor L-tryptophan or monofluoromethyldopa, an inhibitor of the L-aromatic amino acid decarboxylase. The results show that the spontaneous release of 5-hydroxytryptamine and its metabolite reflects largely calcium-dependent exocytotic release of the amine. "Neuronal uptake" (into aminergic and/or enterochromaffin cells) followed by deamination appears to be the main pathway of 5-hydroxytryptamine catabolism in the guinea-pig ileum.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D009197:Myenteric Plexus / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D010477:Perfusion; D011169:Portal Vein; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
D012701:Serotonin; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D014364:Tryptophan; D010293:Pargyline; D007099:Imipramine; D002118:Calcium