Prostaglandin E₂ is a mediator of 5-hydroxytryptamine induced water and electrolyte secretion in the human jejunum

Studies in the rat jejunum in vivo have shown that 5-hydroxytryptamine (5-HT) causes secretion of fluid and luminal release of prostaglandin (PG) E₂. These effects can be blocked by indomethacin and ketanserin, which suggests that PGE₂ may be an important intermediate in the transduction mechanism leading to 5-HT induced fluid secretion. To test this hypothesis in man 'steady state' perfusions (9 ml/min) were done in eight healthy volunteers using the triple lumen technique. The proximal jejunum was perfused with Ringer's solution which contained ⁵¹Cr-EDTA as a non-absorbable marker. Before and after the administration of indomethacin (1.0 mg/kg iv) the effects of exogenous 5-HT (10 μg/kg/min iv) on jejunal net transport of fluid and electrolytes and jejunal flow rate (JFR) of PGE₂ were measured in 15-min periods for 2 x 60 minutes after a 60 minute control period. 5-HT reversed fluid and electrolyte absorption into profuse secretion (p < 0.01, Duncan's multiple range test) and significantly increased JFR of PGE₂ (p < 0.01). Indomethacin partly restored fluid and electrolyte absorption (p < 0.01) and inhibited JFR of PGE₂ (p < 0.05). These results provide further evidence in favour of the theory that PGs are involved in 5-HT induced intestinal fluid secretion.