Evidence for the involvement of 5‐HT4 receptors in the 5‐hydroxytryptamine‐induced pattern of migrating myoelectric complex in sheep

The effects induced by 5‐hydroxytryptamine (5‐HT) on gastrointestinal myoelectric activity in conscious sheep were recorded through electrodes chronically implanted and analysed by computer. The 5‐HT receptors and the cholinergic neuronal pathways involved in these actions were investigated. The intravenous (i.v.) administration of 5‐HT (2, 4 and 8 μg kg−1 min−1, 5 min) induced an antral inhibition concomitant with a duodenal activity front that migrated to the jejunum, followed by a period of intestinal inactivity. This myoelectric pattern closely resembled that observed in the phases III and I of the migrating myoelectric complex (MMC) in sheep. The 0.5 μg kg−1 min−1 dose evoked the same pattern in only two out of the six animals used. Likewise, the 1 μg kg−1 min−1 dose similarly affected four of the six animals. In addition, a transient stimulation was observed in the antrum and jejunum when the two highest doses were used. The 5‐HT1 antagonist, methiothepin (0.1 mg kg−1), the 5‐HT2 antagonists, ritanserin (0.1 mg kg−1) and ketanserin (0.3 mg kg−1), the 5‐HT3 antagonists, granisetron (0.2 mg kg−1) and ondansetron (0.5 mg kg−1), as well as the 5‐HT4 antagonist, GR113808 (0.2 mg kg−1), did not modify the spontaneous gastrointestinal myoelectric activity. However, the cholinoceptor antagonists, atropine (0.2 mg kg−1) and hexamethonium (2 mg kg−1), inhibited gastrointestinal activity. When these antagonists were injected i.v. 10 min before 5‐HT (2 or 4 μg kg−1 min−1, 5 min), only GR113808, atropine and hexamethonium were able to modify the 5‐HT‐induced actions, all of them being completely blocked by the three antagonists. Our data show that 5‐HT initiates a MMC‐like pattern in the gastrointestinal area in sheep through 5‐HT4 receptors. Furthermore, these actions are mediated by cholinergic neural pathways involving muscarinic and nicotinic receptors. However, our results do not indicate a role for either 5‐HT1, 5‐HT2 or 5‐HT3 receptors in the 5‐HT‐induced effects. British Journal of Pharmacology (1997) 120, 1144–1150; doi:10.1038/sj.bjp.0700997