Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal transit in lipopolysaccharide-treated rats

Authors

  • Ronald Mathison,

    1. Gastrointestinal Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    2. Mucosal Inflammation Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Winnie Ho,

    1. Gastrointestinal Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    2. Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    3. Mucosal Inflammation Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Quentin J Pittman,

    1. Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    2. Mucosal Inflammation Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Joseph S Davison,

    1. Gastrointestinal Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    2. Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Keith A Sharkey

    Corresponding author
    1. Gastrointestinal Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    2. Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    3. Mucosal Inflammation Research Groups, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
      Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. E-mail: ksharkey@ucalgary.ca
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Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. E-mail: ksharkey@ucalgary.ca

Abstract

  • The biological effects of cannabinoids (CB) are mediated by CB1 and CB2 receptors. The role of CB2 receptors in the gastrointestinal tract is uncertain. In this study, we examined whether CB2 receptor activation is involved in the regulation of gastrointestinal transit in rats.

  • Basal and lipopolysaccharide (LPS)-stimulated gastrointestinal transit was measured after instillation of an Evans blue-gum Arabic suspension into the stomach, in the presence of specific CB1 and CB2 agonists and antagonists, or after treatment with inhibitors of mediators implicated in the transit process.

  • In control rats a CB1 (ACEA; 1 mg kg−1), but not a CB2 (JWH-133; 1 mg kg−1), receptor agonist inhibited basal gastrointestinal transit. The effects of the CB1 agonist were reversed by the CB1 antagonist AM-251, which alone increased basal transit. LPS treatment increased gastrointestinal transit. This increased transit was reduced to control values by the CB2, but not the CB1, agonist. This inhibition by the CB2 agonist was dose dependent and prevented by a selective CB2 antagonist (AM-630; 1 mg kg−1).

  • By evaluating the inhibition of LPS-enhanced gastrointestinal transit by different antagonists, the effects of the CB2 agonist (JWH-133; 1 mg kg−1) were found to act via cyclooxygenase, and to act independently of inducible nitric oxide synthase (NOS) and platelet-activating factor. Interleukin-1β and constitutive NOS isoforms may be involved in the accelerated LPS transit.

  • The activation of CB2 receptors in response to LPS is a mechanism for the re-establishment of normal gastrointestinal transit after an inflammatory stimulus.

British Journal of Pharmacology (2004) 142, 1247–1254. doi:10.1038/sj.bjp.0705889

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