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Published in: Digestive Diseases and Sciences 6/2012

01-06-2012 | Original Article

The Effects of 5-HT4 Receptor Agonist, Mosapride Citrate, on Visceral Hypersensitivity in a Rat Model

Authors: Jae Woong Lee, Ki Woon Sung, Oh Young Lee, Seo Eun Lee, Chong Il Sohn

Published in: Digestive Diseases and Sciences | Issue 6/2012

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Abstract

Background and Aims

Mosapride citrate is known to affect gastric motility. However, whether mosapride citrate has any effect on visceral pain in the colon or rectum is not certain. The aim of this study was to assess the effects of mosapride citrate on visceral pain in a rat visceral hypersensitivity model.

Methods

The perception of visceral pain was evaluated by the visceromotor response to colorectal distension observed on electromyographs of the abdominal musculature in urethane-anesthetized rats. Visceral hypersensitivity was induced by the intrarectal instillation of 4% acetic acid or 1.5% zymosan. Mosapride citrate was administered intraperitoneally 3 h later. VMRs to CRD were recorded prior to the instillation of acetic acid or zymosan and before and after mosapride citrate treatment.

Results

The intracolonic instillation of acetic acid resulted in a significant increase in VMRs of the abdominal muscles to CRD, compared with the pretreatment state (174 ± 24%, P < 0.05). The intracolonic instillation of zymosan resulted in a significant increase in VMRs of the abdominal muscles to CRD, compared with the pretreatment state (144 ± 9%, P < 0.05). Intraperitoneal injection of mosapride citrate resulted in a significant reduction in the VMRs to CRD in an acetic acid-induced visceral hypersensitivity rat model (61 ± 9%, P < 0.05). The intraperitoneal injection of mosapride citrate also resulted in a significant reduction in the VMRs to CRD in a zymosan-induced visceral hypersensitivity rat model (67 ± 9%, P < 0.05).

Conclusions

Mosapride citrate diminished visceral pain in rats.
Literature
1.
go back to reference Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45:II43–II47.PubMedCrossRef Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45:II43–II47.PubMedCrossRef
2.
go back to reference Ness TJ, Gebhart GF. Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res. 1988;450:153–169.PubMedCrossRef Ness TJ, Gebhart GF. Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res. 1988;450:153–169.PubMedCrossRef
3.
go back to reference Bouin M, Plourde V, Boivin M, et al. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology. 2002;122:1771–1777.PubMedCrossRef Bouin M, Plourde V, Boivin M, et al. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology. 2002;122:1771–1777.PubMedCrossRef
4.
go back to reference Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:125–132.PubMedCrossRef Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut. 1973;14:125–132.PubMedCrossRef
5.
go back to reference Sohn CI, Park HJ, Gebhart GF. Adenosine receptor agonists modulate visceral hyperalgesia in the rat. Gut Liver. 2008;2:39–46.PubMedCrossRef Sohn CI, Park HJ, Gebhart GF. Adenosine receptor agonists modulate visceral hyperalgesia in the rat. Gut Liver. 2008;2:39–46.PubMedCrossRef
6.
go back to reference Briejer MR, Akkermans LM, Schuurkes JA. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev. 1995;47:631–651.PubMed Briejer MR, Akkermans LM, Schuurkes JA. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev. 1995;47:631–651.PubMed
7.
go back to reference Fink C, Tatar M, Failing K, Hospes R, Kressin M, Klisch K. Serotonin-containing cells in the gastrointestinal tract of newborn foals and adult horses. Anat Histol Embryol. 2006;35:23–27.PubMedCrossRef Fink C, Tatar M, Failing K, Hospes R, Kressin M, Klisch K. Serotonin-containing cells in the gastrointestinal tract of newborn foals and adult horses. Anat Histol Embryol. 2006;35:23–27.PubMedCrossRef
8.
go back to reference Costedio MM, Hyman N, Mawe GM. Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum. 2007;50:376–388.PubMedCrossRef Costedio MM, Hyman N, Mawe GM. Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum. 2007;50:376–388.PubMedCrossRef
9.
go back to reference Kim HS, Choi EJ, Park H. The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro. Neurogastroenterol Motil. 2008;20:169–176.PubMedCrossRef Kim HS, Choi EJ, Park H. The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro. Neurogastroenterol Motil. 2008;20:169–176.PubMedCrossRef
10.
go back to reference Carlsson L, Amos GJ, Andersson B, Drews L, Duker G, Wadstedt G. Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: implications for proarrhythmic potential? J Pharmacol Exp Ther. 1997;282:220–227.PubMed Carlsson L, Amos GJ, Andersson B, Drews L, Duker G, Wadstedt G. Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: implications for proarrhythmic potential? J Pharmacol Exp Ther. 1997;282:220–227.PubMed
11.
go back to reference Kanazawa M, Watanabe S, Tana C, Komuro H, Aoki M, Fukudo S. Effect of 5-HT(4) receptor agonist mosapride citrate on rectosigmoid sensorimotor function in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2011;23:754–e332.PubMedCrossRef Kanazawa M, Watanabe S, Tana C, Komuro H, Aoki M, Fukudo S. Effect of 5-HT(4) receptor agonist mosapride citrate on rectosigmoid sensorimotor function in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2011;23:754–e332.PubMedCrossRef
12.
go back to reference Seto Y, Yoshida N, Kaneko H. Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats. J Pharmacol Sci. 2011;116:47–53.PubMedCrossRef Seto Y, Yoshida N, Kaneko H. Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats. J Pharmacol Sci. 2011;116:47–53.PubMedCrossRef
13.
go back to reference Sohn CI. Experimental animal models for the study of visceral pain. Korean J Gastroenterol. 2001;38:77–82. Sohn CI. Experimental animal models for the study of visceral pain. Korean J Gastroenterol. 2001;38:77–82.
15.
go back to reference Müller-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther. 2001;15:1655–1666.PubMedCrossRef Müller-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther. 2001;15:1655–1666.PubMedCrossRef
16.
go back to reference Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde G. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology. 2000;118:463–468.PubMedCrossRef Prather CM, Camilleri M, Zinsmeister AR, McKinzie S, Thomforde G. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology. 2000;118:463–468.PubMedCrossRef
17.
go back to reference Coffin B, Farmachidi JP, Rueegg P, Bastie A, Bouhassira D. Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects. Aliment Pharmacol Ther. 2003;17:577–585.PubMedCrossRef Coffin B, Farmachidi JP, Rueegg P, Bastie A, Bouhassira D. Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects. Aliment Pharmacol Ther. 2003;17:577–585.PubMedCrossRef
18.
go back to reference Schikowski A, Thewissen M, Mathis C, Ross HG, Enck P. Serotonin type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum. Neurogastroenterol Motil. 2002;14:221–227.PubMedCrossRef Schikowski A, Thewissen M, Mathis C, Ross HG, Enck P. Serotonin type-4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum. Neurogastroenterol Motil. 2002;14:221–227.PubMedCrossRef
19.
go back to reference Briejer MR, Schuurkes JA. 5-HT3 and 5-HT4 receptors and cholinergic and tachykininergic neurotransmission in the guinea-pig proximal colon. Eur J Pharmacol. 1996;308:173–180.PubMedCrossRef Briejer MR, Schuurkes JA. 5-HT3 and 5-HT4 receptors and cholinergic and tachykininergic neurotransmission in the guinea-pig proximal colon. Eur J Pharmacol. 1996;308:173–180.PubMedCrossRef
20.
go back to reference McLean PG, Coupar IM. Stimulation of cyclic AMP formation in the circular smooth muscle of human colon by activation of 5-HT4-like receptors. Br J Pharmacol. 1996;117:238–239.PubMed McLean PG, Coupar IM. Stimulation of cyclic AMP formation in the circular smooth muscle of human colon by activation of 5-HT4-like receptors. Br J Pharmacol. 1996;117:238–239.PubMed
21.
go back to reference Mine Y, Yoshikawa T, Oku S, Nagai R, Yoshida N, Hosoki K. Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther. 1997;283:1000–1008.PubMed Mine Y, Yoshikawa T, Oku S, Nagai R, Yoshida N, Hosoki K. Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther. 1997;283:1000–1008.PubMed
22.
go back to reference Yoshida N, Omoya H, Oka M, Furukawa K, Ito T, Karasawa T. AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties. Arch Int Pharmacodyn Ther. 1989;300:51–67.PubMed Yoshida N, Omoya H, Oka M, Furukawa K, Ito T, Karasawa T. AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties. Arch Int Pharmacodyn Ther. 1989;300:51–67.PubMed
23.
go back to reference Sasaki N, Okamura K, Yamada H. Effects of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on electrical activity of the small intestine and cecum in horses. Am J Vet Res. 2005;66:1321–1323.PubMedCrossRef Sasaki N, Okamura K, Yamada H. Effects of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on electrical activity of the small intestine and cecum in horses. Am J Vet Res. 2005;66:1321–1323.PubMedCrossRef
24.
go back to reference Yoshida N, Omoya H, Kato S, Ito T. Pharmacological effects of the new gastroprokinetic agent mosapride citrate and its metabolites in experimental animals. Arzneimittelforschung. 1993;43:1078–1083.PubMed Yoshida N, Omoya H, Kato S, Ito T. Pharmacological effects of the new gastroprokinetic agent mosapride citrate and its metabolites in experimental animals. Arzneimittelforschung. 1993;43:1078–1083.PubMed
25.
go back to reference Lee JW, Park JH, Park DI, et al. Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase. Dig Dis Sci. 2010;55:2922–2928.PubMedCrossRef Lee JW, Park JH, Park DI, et al. Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase. Dig Dis Sci. 2010;55:2922–2928.PubMedCrossRef
26.
go back to reference Cremon C, Carini G, Wang B, et al. Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. Am J Gastroenterol. 2011;106:1290–1298.PubMedCrossRef Cremon C, Carini G, Wang B, et al. Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. Am J Gastroenterol. 2011;106:1290–1298.PubMedCrossRef
27.
go back to reference Hargreaves AC, Lummis SC, Taylor CW. Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. Mol Pharmacol. 1994;46:1120–1128.PubMed Hargreaves AC, Lummis SC, Taylor CW. Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. Mol Pharmacol. 1994;46:1120–1128.PubMed
28.
go back to reference Callahan MJ. Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. J Clin Gastroenterol. 2002;35:S58–S67.PubMedCrossRef Callahan MJ. Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. J Clin Gastroenterol. 2002;35:S58–S67.PubMedCrossRef
29.
go back to reference Talley NJ, Phillips SF, Haddad A, et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci. 1990;35:477–480.PubMedCrossRef Talley NJ, Phillips SF, Haddad A, et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Dig Dis Sci. 1990;35:477–480.PubMedCrossRef
30.
go back to reference Cremonini F, Delgado-Aros S, Camilleri M. Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials. Neurogastroenterol Motil. 2003;15:79–86.PubMedCrossRef Cremonini F, Delgado-Aros S, Camilleri M. Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials. Neurogastroenterol Motil. 2003;15:79–86.PubMedCrossRef
31.
go back to reference Ford AC, Brandt LJ, Young C, Chey WD, Foxx-Orenstein AE, Moayyedi P. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009;104:1831–1843; quiz 1844.PubMedCrossRef Ford AC, Brandt LJ, Young C, Chey WD, Foxx-Orenstein AE, Moayyedi P. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009;104:1831–1843; quiz 1844.PubMedCrossRef
32.
go back to reference Le Bars D, Willer JC, De Broucker T. Morphine blocks descending pain inhibitory controls in humans. Pain. 1992;48:13–20.PubMedCrossRef Le Bars D, Willer JC, De Broucker T. Morphine blocks descending pain inhibitory controls in humans. Pain. 1992;48:13–20.PubMedCrossRef
33.
go back to reference Chitour D, Dickenson AH, Le Bars D. Pharmacological evidence for the involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC). Brain Res. 1982;236:329–337.PubMedCrossRef Chitour D, Dickenson AH, Le Bars D. Pharmacological evidence for the involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC). Brain Res. 1982;236:329–337.PubMedCrossRef
34.
go back to reference Kraus E, Besson JM, Le Bars D. Behavioral model for diffuse noxious inhibitory controls (DNIC): potentiation by 5-hydroxytryptophan. Brain Res. 1982;231:461–465.PubMedCrossRef Kraus E, Besson JM, Le Bars D. Behavioral model for diffuse noxious inhibitory controls (DNIC): potentiation by 5-hydroxytryptophan. Brain Res. 1982;231:461–465.PubMedCrossRef
35.
go back to reference Sivarao DV, Langdon S, Bernard C, Lodge N. Colorectal distension-induced pseudoaffective changes as indices of nociception in the anesthetized female rat: morphine and strain effects on visceral sensitivity. J Pharmacol Toxicol Methods. 2007;56:43–50.PubMedCrossRef Sivarao DV, Langdon S, Bernard C, Lodge N. Colorectal distension-induced pseudoaffective changes as indices of nociception in the anesthetized female rat: morphine and strain effects on visceral sensitivity. J Pharmacol Toxicol Methods. 2007;56:43–50.PubMedCrossRef
36.
go back to reference Laird JM, Martinez-Caro L, Garcia-Nicas E, Cervero F. A new model of visceral pain and referred hyperalgesia in the mouse. Pain. 2001;92:335–342.PubMedCrossRef Laird JM, Martinez-Caro L, Garcia-Nicas E, Cervero F. A new model of visceral pain and referred hyperalgesia in the mouse. Pain. 2001;92:335–342.PubMedCrossRef
37.
go back to reference Lu G, Qian X, Berezin I, Telford GL, Huizinga JD, Sarna SK. Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. Am J Physiol. 1997;273:G1233–G1245.PubMed Lu G, Qian X, Berezin I, Telford GL, Huizinga JD, Sarna SK. Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. Am J Physiol. 1997;273:G1233–G1245.PubMed
38.
go back to reference La JH, Kim TW, Sung TS, Kang JW, Kim HJ, Yang IS. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World J Gastroenterol. 2003;9:2791–2795.PubMed La JH, Kim TW, Sung TS, Kang JW, Kim HJ, Yang IS. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World J Gastroenterol. 2003;9:2791–2795.PubMed
39.
go back to reference Jones RC 3rd, Otsuka E, Wagstrom E, Jensen CS, Price MP, Gebhart GF. Short-term sensitization of colon mechanoreceptors is associated with long-term hypersensitivity to colon distention in the mouse. Gastroenterology. 2007;133:184–194.PubMedCrossRef Jones RC 3rd, Otsuka E, Wagstrom E, Jensen CS, Price MP, Gebhart GF. Short-term sensitization of colon mechanoreceptors is associated with long-term hypersensitivity to colon distention in the mouse. Gastroenterology. 2007;133:184–194.PubMedCrossRef
Metadata
Title
The Effects of 5-HT4 Receptor Agonist, Mosapride Citrate, on Visceral Hypersensitivity in a Rat Model
Authors
Jae Woong Lee
Ki Woon Sung
Oh Young Lee
Seo Eun Lee
Chong Il Sohn
Publication date
01-06-2012
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 6/2012
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-012-2101-z

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