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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/G78    most recent ajpgi.90285.2008v2 ajpgi.90285.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Duncan, M. Articles by Sharkey, K. A. PubMed PubMed Citation Articles by Duncan, M. Articles by Sharkey, K. A.

NEUROREGULATION AND MOTILITY

Cannabinoid CB₂ receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats

¹Snyder Institute of Infection, Immunity and Inflammation and Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; ²Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana; and ³Department of Biological Sciences, California State Polytechnic University, Pomona, California

Submitted 8 April 2008 ; accepted in final form 12 May 2008

Enhanced intestinal transit due to lipopolysaccharide (LPS) is reversed by cannabinoid (CB)₂ receptor agonists in vivo, but the site and mechanism of action are unknown. We have tested the hypothesis that CB₂ receptors are expressed in the enteric nervous system and are activated in pathophysiological conditions. Tissues from either saline- or LPS-treated (2 h; 65 µg/kg ip) rats were processed for RT-PCR, Western blotting, and immunohistochemistry or were mounted in organ baths where electrical field stimulation was applied in the presence or absence of CB receptor agonists. Whereas the CB₂ receptor agonist JWH133 did not affect the electrically evoked twitch response of the ileum under basal conditions, in the LPS-treated tissues JWH133 was able to reduce the enhanced contractile response in a concentration-dependent manner. Rat ileum expressed CB₂ receptor mRNA and protein under physiological conditions, and this expression was not affected by LPS treatment. In the myenteric plexus, CB₂ receptors were expressed on the majority of neurons, although not on those expressing nitric oxide synthase. LPS did not alter the distribution of CB₂ receptor expression in the myenteric plexus. In vivo LPS treatment significantly increased Fos expression in both enteric glia and neurons. This enhanced expression was significantly attenuated by JWH133, whose action was reversed by the CB₂ receptor antagonist AM630. Taking these facts together, we conclude that activation of CB₂ receptors in the enteric nervous system of the gastrointestinal tract dampens endotoxin-induced enhanced intestinal contractility.

gastrointestinal motility; Fos expression; myenteric plexus; cannabinoids