Adrenergic modulation of the release of 5-hydroxytryptamine from the vascularly perfused ileum of the guinea-pig

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Abstract
1 Isolated segments of the guinea-pig ileum were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by h.p.l.c. with electrochemical detection. Test substances were applied via the arterial perfusion medium. 2 Isoprenaline (0.1 μm) increased the outflow of 5-HT and 5-HIAA maximally by about 75% and this was antagonized by propranolol (0.1 μm). Forskolin (1–10 μm) increased the outflow of 5-HT by approximately 105% and that of 5-HIAA by approximately 55%. The phosphodiesterase inhibitor AH 21–132 (0.1–1 μm) increased the outflow of 5-HT and 5-HIAA by about 70%. Isoprenaline (1 nm) and AH 21–132 (10 nm), which alone had no effect, increased the outflow of 5-HT and 5-HIAA by 75%, when applied in combination. 3 Clonidine (1 μm) reduced the outflow of 5-HT by 45%, an effect blocked by tolazoline (1 μm), but not by prazosin (0.1μm). 4 The effects of isoprenaline, forskolin and clonidine were also observed in the presence of tetrodotoxin (1 μm) demonstrating a direct modulation of 5-HT release from the enterochromaffin cells. 5 In conclusion, the release of 5-HT from enterochromaffin cells is facilitated by activation of β-adrenoceptors and inhibited via α2-adrenoceptors. Enhancing intracellular cyclic AMP, by direct stimulation of adenylate cyclase with forskolin or by inhibition of phosphodiesterase, also facilitates the release of 5-HT. The β-adrenoceptor-mediated effect on 5-HT release appears to involve an increase in cyclic AMP, as the effect of isoprenaline was potentiated after inhibition of phosphodiesterase.