GABA receptors are involved in the modulation of the release of 5-hydroxytryptamine from the vascularly perfused small intestine of the guinea-pig.

Isolated small intestinal segments of the guinea-pig were perfused arterially and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Muscimol (1 microM) time dependently first increased then decreased the release of 5-HT and 5-HIAA. The stimulatory effect was prevented by tetrodotoxin (TTx) or scopolamine, indicating that it was mediated by the release of acetylcholine. Bicuculline concentration dependently decreased (1 microM) or increased (10, 50 microM) the release of 5-HT and 5-HIAA, indicating that endogenous GABA also activates stimulatory and inhibitory GABAA receptors. Bicuculline antagonized the stimulatory and inhibitory effect of muscimol. (-)-Baclofen, but not its (+) enantiomer, inhibited the release of 5-HT in the absence and presence of TTx. It was concluded that the release of 5-HT from enterochromaffin cells is directly inhibited by GABAA and GABAB receptors. In addition, acetylcholine released after activation of GABAA receptors stimulates 5-HT release.