Oral ingestion of a 5-HT4 receptor agonist evokes a CNS-ENS mediated gastro-colonic reflex involving High Amplitude Propulsive Contractions (HAPCs) in the human colon within 5minutes

Assessment of neurogenic colon motor functions is a challenge since the colon may not show activity for long periods of time. Appropriate stimuli are required during assessment in order to evaluate myogenic and neurogenic functions or abnormalities. We performed high-resolution manometry using 36 solid-state sensors, 1 cm apart in 15 patients with chronic constipation or IBS-D and volunteers. Oral prucalopride is rapidly absorbed independent of food intake and maximal bioavailability is reached within 1-3 hours (1). Oral prucalopride (2 mg) had a biphasic effect. A first excitation of the colon musculature was seen within the first 20 min, and a second excitation was seen after 40 – 90 min. The first excitation produced an HAPC in 4 of 17 subjects studied at 4.1 ± 1.1 min after ingestion; or an increase in haustral boundary contractions (HC) and/or simultaneous contractions (SC) in 7/17 was observed at 7.8 ± 3.1 min. The second excitation consisted of HAPCs in 4 out of 15 studied, at 58.0 ± 4.8 min, or HC and SCs in 11/15 at 45 ± 10 min. In all 17 subjects, baseline HAPCs were never observed and in only 1 subject an HAPC occurred after a meal. We infer that prucalopride affects 5-HT4 receptors on gastric or duodenal enterochromaffin cells (2) to elicit a CNS-ENS mediated gastro-colonic reflex in addition to its prokinetic effect observed after full bioavailability is reached. Prucalopride therefore may be useful as a test substance to evaluate the ability to generate 5-HT4 mediated neurogenic motor patterns in the human colon. Supported by grants from the National Natural Science Foundation of China and the Canadian Institutes of Health Research.