Abundant 5‐HT Release from EC Cells Disrupts Colonic Motility

Abstract

Serotonin (5‐HT) that is synthesized by enterochromaffin (EC) cells in the intestinal mucosa can activate the ascending contractile and descending relaxant limbs of the peristaltic reflex. However, recent studies have demonstrated that peristalsis persists in the absence of mucosal 5‐HT, raising the question of whether mucosal 5‐HT actually influences propulsive motility. In this study we evaluated the actions of emetic drugs (ipecac, emetine and cisplatin), which are known to induce massive release of 5‐HT from EC cells, on propulsive motility in isolated segments of guinea pig distal colon. A Gastrointestinal Motility Monitor (GIMM; Catamount Research) system was used to record and analyze the rate of fecal pellet propulsive motility. Following a 30 minute equilibration period, pellet velocity was evaluated over three trials separated by 5 minute rest periods, and under control conditions was typically in the range of 1.8‐2.4 mm/sec. Drugs were then added to the solution for 10 min, and an additional 3 trials were recorded. Intraluminal infusion of ipecac (2‐10%), emetine (1‐10mM) or cisplatin (3µM‐1mM) to the bath slowed motility in a concentration‐dependent manner, and halted transit at high concentrations. Bath application of the 5HT3/5HT4 antagonist SDZ‐205‐557 hydrochloride (10µM) inhibited the effects of the emetic compounds, but intraluminal application of the antagonist had no effect. In summary, extensive activation of 5‐HT release from EC cells over an entire segment of the colon has a negative impact on propulsive motility. These findings support the concept that release of mucosal 5‐HT can influence propulsive motility in the intestines. Supported by DK62267