Gastrointestinal Models: Intestinal Transit, Gastric Emptying, and Ulcerogenic Activity in the Rat

Philippe Guillaume1, Daniel Provost1, Pierre Lacroix1

1 Porsolt and Partners Pharmacology, Boulogne‐Billancourt, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.3
DOI:  10.1002/0471141755.ph0503s42
Online Posting Date:  September, 2008
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Abstract

The protocols described in this unit are designed to assess the effects of substances on intestinal transit and gastric emptying and to evaluate their ulcerogenic potential on the stomach and duodenum of the rat. Examples of results obtained with atropine or morphine (intestinal transit), loperamide (gastric emptying), or indomethacin (ulcerogenic activity) used as reference substances are provided for illustrative purposes. Atropine and morphine clearly reduce intestinal transit. Atropine, morphine, and loperamide clearly reduce gastric emptying. Indomethacin shows a marked ulcerogenic potential. Curr. Protoc. Pharmacol. 42:5.3.1‐5.3.12. © 2008 by John Wiley & Sons, Inc.

Keywords: animal models of disease; safety pharmacology; gastrointestinal tract; intestinal transit; gastric emptying; ulcerogenic activity

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Measurement of Intestinal Transit and Gastric Emptying in the Rat
  • Basic Protocol 2: Measurement of Gastric Emptying in the Rat
  • Basic Protocol 3: Measurement of Ulcerogenic Activity in the Rat
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Measurement of Intestinal Transit and Gastric Emptying in the Rat

  Materials
  • Male Wistar rats, 2 to 3 months old, 200 to 220 g at the beginning of the experiment
  • Test compound
  • 0.5% (w/v) carboxymethylcellulose sodium (CMC; Cooper)
  • 0.8 mg/ml atropine sulfate (Sigma)
  • 4.8 mg/ml morphine hydrochloride (optional; Cooper; controlled substance, subject to regulation)
  • Charcoal suspension (see recipe)
  • Physiological saline: 0.9% (w/v) NaCl
  • Polypropylene cage with 1032‐cm2 floor area
  • Animal balance accurate to 1 g (e.g., Sartorius)
  • Permanent waterproof markers, one color for each experimental group
  • Wire mesh grid to fit bottom of 1032‐cm2 floor‐area cage described above
  • 1‐ml syringes (e.g., Terumo)
  • 5‐ml syringes (e.g., Terumo)
  • 7.5‐cm luer gastric probe with olive (4‐mm‐diam.) extremity (Polylabo)

Basic Protocol 2: Measurement of Gastric Emptying in the Rat

  Materials
  • Male Wistar rats, 2 to 3 months old, 200 to 220 g at the beginning of the experiment
  • Test compound
  • 0.5% (w/v) carboxymethylcellulose sodium (CMC; Cooper)
  • 1.6 mg/ml loperamide hydrochloride (Sigma)
  • Phenol red (see recipe)
  • 0.1 and 1 M NaOH
  • 7.4% (w/v) trichloroacetic acid
  • Polypropylene cage with 1032‐cm2 floor area
  • Animal balance accurate to 1 g (e.g., Sartorius)
  • Permanent waterproof markers, one color for each experimental group
  • Wire mesh grid to fit bottom of 1032‐cm2 floor‐area cage described above
  • 1‐ml syringes (e.g., Terumo)
  • 5‐ml syringes (e.g., Terumo)
  • 7.5‐cm luer gastric probe with olive (4‐mm‐diam) extremity (Polylabo)
  • Centrifuge
  • Spectrophotometer

Basic Protocol 3: Measurement of Ulcerogenic Activity in the Rat

  Materials
  • Male Wistar rats, 2 to 3 months old, 200 to 220 g at the beginning of the experiment
  • Test compound
  • 0.5% (w/v) carboxymethylcellulose sodium (CMC; Cooper)
  • Indomethacin (Sigma)
  • 0.01 M sodium carbonate
  • Test compound
  • Polypropylene cage with 1032‐cm2 floor area
  • Permanent waterproof markers, one color for each experimental group
  • Animal balance accurate to 1 g (e.g., Sartorius)
  • 5‐ml syringe (e.g., Terumo)
  • 7.5‐cm Luer gastric probes with olive (4‐mm‐dia.) extremity
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Figures

Videos

Literature Cited

Literature Cited
   Allen, A. 1981. Structure and function of gastrointestinal mucus. In Physiology of the Gastrointestinal Tract, Volume I (R.L. Johnson, ed.) pp. 617‐639. Raven Press, New York.
   Bickel, M. and Kauffman, G.L. 1981. Gastric mucus gel thickness: Effect of distension, 16,16‐dimethyl prostaglandin E2 and carbenoxolone. Gastroenterology 80:770‐775.
   Bolton, J.P., Palmer, D., and Cohen, M.M. 1978. Stimulation of mucus and non‐parietal cell secretion by the E2 prostaglandins. Am. J. Dig. Dis. 23:359‐364.
   Fichelle, J. 1971. Mesure du transit intestinal chez le rat. J. Pharmacol. (Paris) 2:85‐86.
   Flemstrom, G. and Garner, A. 1982. Gastroduodenal HCO3(‐) transport: Characteristics and proposed role in acidity regulation and mucosal protection. Am. J. Physiol. 242:G183‐G193.
   Johansson, C. and Kollberg, B. 1979. Stimulation by intragastrically administered E2 prostaglandins of human gastric mucus output. Eur. J. Clin. Invest. 9:229‐232.
   Lwoff, J.M. 1971. Activité ulcerigene chez le rat. J. Pharmacol. (Paris) 2:81‐83.
   Macht, D.I. and Barba‐Gose, J. 1931. Two methods for pharmacological comparison of insoluble purgatives. J. Am. Pharmacol. Assoc. 20:558‐564.
   McQueen, S., Hutton, D., Allen, A., and Garner, A. 1983. Gastric and duodenal surface mucus gel thickness in rats: Effects of prostaglandins and damaging agents. Am. J. Physiol. 245:G388‐G393.
   Menguy, R. and Masters, Y.F. 1965. The effects of aspirin on gastric mucus secretion. Surg. Gynecol. Obstet. 92:1‐17.
   Robert, A. and Nezamis, J.E. 1958. Ulcerogenic property of steroids. Proc. Soc. Exp. Biol. Med. 99:443‐447.
   Scarpignato, C., Capovilla, T., and Bertaccini, G. 1980. Action of caerulein on gastric emptying of the conscious rat. Arch. Int. Pharmacodyn. Ther. 246:286‐294.
   Van Nueten, J.M., Geivers, H., Fontaine, H., and Janssen, P.A.J. 1973. An improved method for studying peristalsis in the isolated guinea‐pig ileum. Arch. Int. Pharmacodyn. Ther. 203:411‐414.
   Yoshikawa, T., Kawashima, K., and Yoshida, N. 2002. Influence of various drugs on gastric emptying in rats and improving the effects of mosapride citrate, a gastroprokinetic agent. Yakuri to Chiryo/Jpn. Pharm. Ther. 30:979‐984.
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