Endocannabinoid modulation of jejunal afferent responses to LPS.
Summary of "Endocannabinoid modulation of jejunal afferent responses to LPS."
Backgroundâ€‚ Endocannabinoids influence immune function and nociceptive signaling. This study examines cannabinoid modulation of sensory signaling from the GI tract following an acute inflammatory response triggered by systemic administration of bacterial lipopolysaccharide (LPS). Methodsâ€‚ A segment of proximal jejunum was intubated, to measure intraluminal pressure, in anesthetized rats. Afferent impulse traffic was recorded from a single isolated paravascular nerve bundle supplying the jejunal loop. Drugs and LPS were administered intravenously and changes in afferent firing were determined. Key Resultsâ€‚ The non-selective cannabinoid agonist, WIN55,212-2 (1â€ƒmgâ€ƒkg(-1) i.v.) and the anandamide transport inhibitor, VDM11 (1â€ƒmgâ€ƒkg(-1) i.v.) but not the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3â€ƒmgâ€ƒkg(-1) ) caused a significant increase in afferent activity. The WIN55,212-2-induced afferent response was mediated by activation of CB(1) receptors whereas the VDM11 response was mediated by both CB(1) and CB(2) receptor mechanisms. LPS (10â€ƒmgâ€ƒkg(-1) ) evoked an increase in afferent activity which was significantly reduced in the presence of WIN55,212-2 and VDM11 but not URB597. The inhibitory effect of WIN55,212-2 was prevented by CB(1) but not CB(2) receptor antagonism. In contrast, the inhibitory effect of VDM11 remained unaltered after CB(1) or CB(2) receptor blockade. Conclusions & Inferencesâ€‚ Endocannabinoids play a role in modulating afferent signaling and may represent a target for the treatment of visceral hypersensitivity. In contrast to the effects of blocking endocannabinoid uptake (VDM11), inhibiting breakdown of endocannabinoids (URB597) had no effect on baseline or LPS induced afferent firing. Therefore, uptake of cannabinoids rather than breakdown via FAAH terminates their action in the GI tract.
University of Sheffield, Department of Biomedical Sciences, Sheffield, UK University of Nottingham, Department of Biomedical Science, Nottingham, UK.
This article was published in the following journal.
Name: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22734449
- DOI: http://dx.doi.org/10.1111/j.1365-2982.2012.01961.x
Medical and Biotech [MESH] Definitions
Afferent Loop Syndrome
A complication of gastrojejunostomy (BILLROTH II PROCEDURE), a reconstructive GASTROENTEROSTOMY. It is caused by acute (complete) or chronic (intermittent) obstruction of the afferent jejunal loop due to HERNIA, intussusception, kinking, VOLVULUS, etc. It is characterized by PAIN and VOMITING of BILE-stained fluid.
Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers.
Loss of detectable antigen from the surface of a cell after incubation with antibodies. This is one method in which some tumors escape detection by the immune system. Antigenic modulation of target antigens also reduces the therapeutic effectiveness of treatment by monoclonal antibodies.
Pathological development in the JEJUNUM region of the SMALL INTESTINE.
Tumors or cancer in the JEJUNUM region of the small intestine (INTESTINE, SMALL).
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