Elsevier

Autonomic Neuroscience

Volume 133, Issue 2, 30 May 2007, Pages 136-145
Autonomic Neuroscience

Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats

https://doi.org/10.1016/j.autneu.2006.11.002Get rights and content

Abstract

Wood creosote has been used as an herbal medicine against acute diarrhea caused by food poisoning and has an inhibitory effect on colonic motility and enterotoxin-induced ion secretion. Since no previous studies have examined the effects of wood creosote on stress-induced alteration of colonic motility, we examined the effects on the colonic motility altered by intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key mediator in responses to stress. We recorded motor activity in proximal and distal colon of unrestrained conscious rats via two manometory catheters. The frequencies of phase III-like contraction and the % motor indices in both proximal and distal colon were measured. At the same time the number of fecal pellets excreted was counted. I.c.v. injection of CRF increased the motor activity in both proximal and distal colon, and these effects were completely antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed by intravenously administered wood creosote. Intraluminal administration of the 5-HT3 receptor antagonist granisetron, or the 5-HT4 receptor antagonist SB 204070 blocked the increase in colonic motility induced by i.c.v. injection of CRF. Wood creosote prevented the increase in colonic motility induced by the 5-HT3 receptor agonist SR57227A in the proximal colon, while it prevented the increase in colonic motility induced by the 5-HT4 receptor agonist RS67506 in the distal colon. These results indicate that wood creosote prevents the increase in colonic motility induced by CRF via 5-HT3 receptors in the proximal colon, and via 5-HT4 receptors in the distal colon, suggesting that wood creosote might be useful to treat stress-induced diarrhea.

Introduction

Corticotropin-releasing factor (CRF) is a 41-amino acid hypothalamic peptide and a major regulator of the hypothalamic–pituitary–adrenal (HPA) axis contributing to endocrine, autonomic, immunologic, and behavioral responses to stress (Chrousos, 1995, Vale et al., 1981). Two types of receptors, CRF receptor type 1 and type 2 have been identified and their actions have been widely investigated (Bampton et al., 2001, Liaw et al., 1996, Lovenberg et al., 1995). The intracerebroventricular (i.c.v.) injection of CRF in rats has been reported to suppress gastric emptying of solid nutrient meal via CRF type 2 receptors (Martínez et al., 1998) and stimulate defecation via CRF type 1 receptors (Martínez and Taché, 2001). On the other hand, it has been shown that stress-induced alterations of the GI motility, such as decreased gastric emptying and increased colonic motility are blocked by CRF type 2 receptor antagonists and CRF type 1 receptor antagonists, respectively (Martínez and Taché, 2001, Taché et al., 2001).

Wood creosote is a major component of Seirogan™ that has been used as a remedy for acute diarrhea caused by food poisoning for more than one hundred years in Japan. Wood creosote (CAS no. 8021-39-4) is an herbal medication obtained from fractional distillation of wood tar produced by fume of beech wood. Wood creosote does not cause any serious adverse events in healthy subjects according to the regulation of FDA and has no carcinogenicity in an animal study (Kuge et al., 2001, Kuge et al., 2003). In animal experiments, wood creosote reversed the altered ion-secretion in the intestinal mucosa induced by heat-labile or heat-stable Escherichia coli enterotoxin and also reversed the altered intestinal motility by electrical stimulation, mechanical stimulation with the insertion of glass beads into the distal colon, or acetylcholine administration (Ogata et al., 1993, Ogata et al., 1999, Ataka et al., 1996). Recently, it has been shown that wood creosote normalizes the altered ion secretion induced by restraint stress in rats (Ataka et al., 2003). However no previous studies have examined the effects of wood creosote on stress-related alterations of colonic motility.

In the present study we aimed to examine the effects of intravenous wood creosote on CRF-induced alterations of colonic motility. We used manometric measurements for the pressure waves in the colon of freely moving conscious rats (Ferre and Ruckebusch, 1985, Fujimiya et al., 2000), because this method seems to be appropriate to examine the effects of i.c.v. injected CRF on the physiological state of colonic motility. Involvement of 5-HT receptors mediating the action of wood creosote to prevent CRF-induced alteration of colonic motility was also examined, because 5-HT3 and 5-HT4 receptors are well known to mediate colonic motor activity.

Section snippets

Animals

Male Wistar Hannover GALAS rats (Clea Japan, Tokyo, Japan), weighing 200–250 g were housed at two per cage under conditions of controlled illumination (12:12-h light–dark cycle; lights on 8:00 AM and off at 8:00 PM), humidity (44–46%), and temperature (22–24 °C), with free access to a standard rat diet (CE-2; Clea Japan) and water. All protocols were approved by Shiga University of Medical Science's Animal Welfare Committee.

Preparation of drugs

Wood creosote (TA-03) supplied by Taiko Pharmaceutical Co., Ltd.

Recordings of basal pressure waves in the proximal and distal colon

Cyclic changes of pressure waves were detected in both proximal and distal colon (Fig. 1). The pressure waves consist of the quiescence period during which relatively low amplitude contractions occur, followed by a grouping of strong contractions (phase III-like contractions, shown as arrowheads). Phase III-like contractions were defined as clusters of strong contractions with an amplitude of more than 10 cm H2O accompanied with an elevation of baseline lasting at least 3 min in the proximal

Discussion

To evaluate the colonic motor activity in vivo, manometric measurements for the pressure waves have been preferentially used in human study (Bampton et al., 2001, Rao et al., 2001, Scott, 2003). In animal experiments, on the other hands, most of the previous studies have used the strain gauge transducer to measure the myoelectrical activity in the colon of dogs (Sarna, 1986, Sarna et al., 1984) or rats (Ferre and Ruckebusch, 1985, Li et al., 2002), however a few study has applied the manometric

References (41)

  • V. Martínez et al.

    Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats

    Brain Res.

    (2001)
  • C.J. Steadman et al.

    Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study

    Mayo Clin. Proc.

    (1992)
  • K. Ataka et al.

    Suppression of enterotoxin-induced intestinal fluid secretion by wood creosote

    Res. Commun. Mol. Pathol. Pharmacol.

    (1996)
  • K. Ataka et al.

    Seirogan (wood creosote) inhibits stress-induced secretion in rat intestinal epithelium

    Dig. Dis. Sci.

    (2003)
  • M.B. Bampton et al.

    Prolong multi-point recording of colonic manometry in the unprepared human colon: providing insight into potentially relevant pressure wave parameters

    Am. J. Gastroenterol.

    (2001)
  • G.P. Chrousos

    The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation

    N. Engl. J. Med.

    (1995)
  • T. Croci et al.

    Manometric patterns of rat colonic motor activity and defecation: effect of selective 5HT1A agonist 8-OH-DPAT

    Dig. Dis. Sci.

    (1994)
  • J.P. Ferre et al.

    Myoelectrical activity and propulsion in the large intestine of fed and fasted rats

    J. Physiol. (Lond.)

    (1985)
  • M. Fujimiya et al.

    Neuropeptide Y induces fasted pattern of duodenal motility via Y2 receptors in conscious fed rats

    Am. J. Physiol.: Gasterointest. Liver Physiol.

    (2000)
  • K. Fujino et al.

    Ghrelin induced fasted motor activity of the gastrointestinal tract in conscious fed rats

    J. Physiol.

    (2003)
  • S. Fukumoto et al.

    Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats

    Am. J. Physiol., Regul. Integr. Comp. Physiol.

    (2003)
  • M.D. Gershon

    Nerves, refrexes, and the enteric nervous system pathogenesis of the irritable bowel syndrome

    J. Clin. Gastroenterol.

    (2005)
  • K. Haga et al.

    The function of 5-HT3 receptors on colonic transit in rats

    Obes. Res.

    (1995)
  • C. Ito et al.

    Effect of GK-128 [2-[2-methylimidazol-1-yl]methyl]-benzo[f]thiochromen-1-one monohydrochloride hemihydrate], a selective 5-hydroxytryptamine3 receptor antagonist, on colonic function in rats

    J. Pharmacol. Exp. Ther.

    (1997)
  • N. Kihara et al.

    Effect of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats

    Am. J. Physiol.: Gasterointest. Liver Physiol.

    (2001)
  • T. Kuge et al.

    Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague–Dawley rats

    Int. J. Toxicol.

    (2001)
  • T. Kuge et al.

    Multiple-dose escalation, safety, and tolerability study of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in healthy subjects

    J. Clin. Pharmacol.

    (2003)
  • C.W. Liaw et al.

    Cloning and characterization of the human corticotropin-releasing factor-2 receptor

    Endocrinology

    (1996)
  • M. Li et al.

    Cholinergic and nitrergic regulation of in vivo giant migrating contractions in rat colon

    Am. J. Physiol.: Gasterointest. Liver Physiol.

    (2002)
  • T.W. Lovenberg et al.

    Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain

    Proc. Natl. Acad. Sci. U. S. A.

    (1995)
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