Serotonin stimulates migrating myoelectric complex via 5-HT3-receptors dependent on cholinergic pathways in rat small intestine.

Abstract

We have investigated the effect of 5-hydroxytryptamine (5-HT) and different 5-HT-receptor antagonists and atropine on the migrating myoelectric complex in the rat small intestine. Infusion of 5-HT dose-dependently shortened the interval between phase III of the migrating myoelectric complex (MMC). In untreated animals the interval in upper jejunum was 19.1 (16.0-22.1) min. At doses of 10 and 20 nmol kg-1 min-1, the interval decreased to 15.2 (12.0-18.4) and 10.2 (9.4-11.0) min, respectively. The 5-HT3-receptor antagonist ondansetron (0.5 mg kg-1) alone increased the MMC interval from 20.8 (15.1-26.5) to 33.9 (19.4-48.4) min. Neither methiothepin (0.5 mg kg-1) nor ketanserin (0.5 mg kg-1), selective for 5-HT1/5-HT2- and 5-HT2-receptors, respectively, changed the MMC interval. The 5-HT4-receptor antagonist GR 113808 (0.5 mg kg-1) disrupted the MMC and induced irregular spiking activity. Ondansetron and atropine antagonized the 5-HT-induced shortening of the MMC interval. Neither methiothepin nor ketanserin affected the response to 5-HT. GR 113808 did not block the response to 5-HT in half of the animals; however, in the remaining ones MMC was disrupted and irregular spiking induced. In conclusion, these results show that 5-HT dose-dependently stimulates the cycling of the MMC in the small intestine via 5-HT3-receptors and a cholinergic final pathway. Our findings encourage further studies on the role of the 5-HT3-receptor in the control of gastrointestinal motility.