5-Hydroxytryptamine (5-HT) has been shown to cause a consistent secretory effect in the rat small intestine only when administered luminally or by close intraarterial infusion. Intraluminal 5-HT-induced secretion is possibly mediated by 5-HT4 receptors. Therefore, it was decided to investigate the effect of 5-HT and selective 5-HT4 receptor agonists (SC 53116 and DAU 6236) on intestinal fluid transport in rat jejunum and ileum. The study also investigated the effect of a selective 5-HT4 receptor antagonist (GR 113808) against the intraluminally administered 5-HT. 2. 5-HT receptor agonists and antagonists were administered intraluminally in pentobarbitone-anesthetized rats. Changes in intestinal fluid transport across the intestinal wall were measured by a single pass technique. 3. Intraluminal 5-HT produced significant antiabsorptive effects is both the jejunum and ileum. The 5-HT-induced responses were blocked by intraluminal administration of the 5-HT4 receptor antagonist GR 113808. The 5-HT4 agonist SC 53116 induced antiabsorptive effects in both regions of the small intestine, but DAU 6236 did not affect the rates of fluid transport. 4. The results indicate that a 5-HT4 receptor has a role in the luminal 5-HT-induced antiabsorptive effect on intestinal fluid transport in the rat.
