Tropisetron and octreotide reduce serotonin-induced fluid hypersecretion in pig jejunum

In vitro data suggest that the serotonin receptor subtype 4 (5-HT4) mediate part of the serotonin (5-HT)-induced intestinal secretion. This study elucidates the involvement of the intestinal 5-HT4 receptor subtype and the anti-diarrhoeal therapeutic potentials of tropisetron and octreotide in 5-HT-induced intestinal hypersecretion in vivo. The effects of intraluminal 5-HT, 5-methoxytryptamine, and tropisetron (ICS 205-930), and subcutaneous octreotide (SMS 201-995) on fluid hypersecretion (accumulation) was studied in tied-off loops in pig jejunum. 5-HT, 5-methoxytryptamine (5-HT4 agonist), and tropisetron (5-HT3/5-HT4 antagonist) all induced a dose-dependent hypersecretion. Low doses of tropisetron reduced, while high doses of tropisetron enhanced the 5-HT and 5-methoxytryptamine responses. Taking into account the hypersecretory effect by itself, tropisetron seemed to completely block the hypersecretory effects of 5-HT and 5-methoxytryptamine. Finally, octreotide reduced the hypersecretory effect of 5-HT, maximally by 30%. These results suggest the involvement of the intestinal 5-HT4 receptor subtype in 5-HT-induced hypersecretion in pig jejunum in vivo. Furthermore, this study demonstrates a potential therapeutic value for octreotide in 5-HT-related diarrhoeagenic disorders in the pig.