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

H. S. Kim, E. J. Choi, HyoJin Park

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Mosapride citrate (mosapride), a substituted benzamide, is a selective 5-HT4 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-HT4 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-HT4 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-HT4 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-HT4 receptors may support these findings. Therefore, mosapride may be a useful alternative to tegaserod and cisapride for constipation.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalNeurogastroenterology and Motility
Volume20
Issue number2
DOIs
Publication statusPublished - 2008 Feb 1

Fingerprint

Guinea Pigs
Colon
Receptors, Serotonin, 5-HT4
Myenteric Plexus
In Vitro Techniques
mosapride
Serotonin 5-HT4 Receptor Agonists
Cisapride
Muscles
Tetrodotoxin
Anal Canal
Constipation
Baths
Atropine
Feces
Electric Stimulation
Stomach
Software
Perfusion
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

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abstract = "Mosapride citrate (mosapride), a substituted benzamide, is a selective 5-HT4 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-HT4 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-HT4 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-HT4 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-HT4 receptors may support these findings. Therefore, mosapride may be a useful alternative to tegaserod and cisapride for constipation.",
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The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro. / Kim, H. S.; Choi, E. J.; Park, HyoJin.

In: Neurogastroenterology and Motility, Vol. 20, No. 2, 01.02.2008, p. 169-176.

Research output: Contribution to journalArticle

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