The effect of mosapride citrate on proximal and distal colonic motor function in the guinea‐pig in vitro

Abstract

Mosapride citrate (mosapride), a substituted benzamide, is a selective 5-HT(4) receptor agonist, and is known to have prokinetic properties on the stomach. However, it is unclear whether mosapride also has a prokinetic effect on the colon. We previously found that mosapride significantly shortened colonic transit time in the guinea-pig, an animal with a distribution of colonic 5-HT(4) receptors similar to that of a human. So, we aimed to separately evaluate the effect of mosapride on proximal and distal colonic motor function in the guinea-pig. Proximal (approximately 8 cm from the ileocolic junction) and distal colon (approximately 8 cm from the anus) were removed. Both ends of the colon were connected to a chamber containing a Krebs-Henseleit solution. To measure colonic transit time, artificial faeces were inserted into the oral side of the lumen and moved towards the anal side by intraluminal perfusion via a peristaltic pump. A total of 6 cm of transit was observed and time was measured in 2 cm increments. A tissue bath study, using electrical stimulation, was performed to estimate the contractile activity of the circular musculature of the colon. Immunohistochemical staining for 5-HT(4) receptors was performed in the myenteric plexus and circular muscle in both proximal and distal colon, and the stained area was measured using a microscope and computer software. Mosapride enhanced contraction at 10(-9) to 10(-7) mol L(-1), coinciding with rapid transit both in proximal and distal colon. This pattern was more prominent in proximal colon. At the high dose (10(-6) mol L(-1)) mosapride had little or no effect on colonic contraction. This stimulatory effect was attenuated by GR113808, atropine and tetrodotoxin. In the myenteric plexus, the density of 5-HT(4) receptors was significantly greater in the proximal colon than in the distal colon, but in circular muscle the density was greater in the distal colon. Thus, mosapride accelerates transit through increased contraction in the proximal colon more than distal colon. The different distribution of neuronal and muscular 5-HT(4) receptors may support these findings. Therefore, mosapride may be a useful alternative to tegaserod and cisapride for constipation.

5-Hydroxytryptamine4 receptor agonists and colonic motility

“…This result differed from the primary data on mosapride (Table 1). We also found that mosapride significantly increased contractile amplitude in the proximal colon, coinciding with rapid transit (Kim et al, 2008). This increased contraction might physiologically expel the proximal stored contents into the distal portion.…”

“…The localization of 5-HT4 receptors in the human colon shows the same pattern as that in the guinea pig (Sakurai-Yamashita et al, 1999). 5-HT4 receptors are more densely distributed in the myenteric plexus in the proximal colon than in the distal colon (Kim et al, 2008). However, in circular muscle, the receptors are more abundant in the distal colon than in the proximal colon.…”

Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

“…16 A baseline 1 g of tension was loaded onto the circular muscle strip during the 60 minutes equilibrium period. 17,18 Electrical field stimulation was conducted to estimate contraction of each organ using a stimulator (Grass S88; Astro-Med, West Warwick, RI, USA). Based on the methods used in other studies, the detailed conditions of electrical field stimulation were as follows: antrum (1 millisecond pulse duration, 80 V, for 10 seconds); jejunum (1 millisecond pulse duration, 60 V, for 10 seconds); ileum (0.5 milliseconds pulse duration, 60 V, for 10 seconds); and proximal colon (0.5 milliseconds pulse duration, 60 V, for 10 seconds) in a stepwise-increment of frequency (2,4,8,and 16 Hz).…”

Effect of Mosapride Citrate Hydrate on the Colon Cleansing Action of Polyethylene Glycol Electrolyte Lavage Solution (PEG-ELS) in Guinea Pigs

“…It is reported that mosapride administered intragastrically at doses of 3 -30 mg/kg significantly enhances colonic motility in conscious guinea pigs implanted with force transducers (21). It is also reported that mosapride accelerates proximal and distal colonic transit or peristalsis in vitro in guinea pigs (23). These results indicate that the stimulatory effect of mosapride on colonic transit is due to accelerated colonic motility and peristalsis in guinea pigs.…”