QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McVey, D. C. Articles by Vigna, S. R. Search for Related Content PubMed PubMed Citation Articles by McVey, D. C. Articles by Vigna, S. R.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Endocannabinoids Induce Ileitis in Rats via the Capsaicin Receptor (VR1)

Departments of Cell Biology and Medicine, Duke University Medical Center, Veterans Affairs Medical Center, Durham, North Carolina (D.C.M, S.R.V.); and the Hormel Institute, University of Minnesota, Austin, Minnesota (P.C.S, H.H.O.S.)

Intraluminal administration of the endocannabinoids N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) causes inflammation similar to that caused by Clostridium difficile toxin A in the rat ileum. The effects of anandamide and 2-AG were significantly inhibited by pretreatment with the specific capsaicin receptor (vanilloid receptor subtype 1; VR1) antagonist capsazepine. Pretreatment with the CB1 and CB2 cannabinoid receptor antagonists N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716) and N-[1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) did not affect the responses to anandamide. It has previously been shown that intraluminal toxin A stimulates substance P (SP) release from primary sensory neurons and that pretreatment with SP receptor [neurokinin (NK)-1 receptor] antagonists inhibits the inflammatory effects of toxin A. Anandamide stimulated SP release and this was blocked by capsazepine pretreatment. Also, pretreatment with the specific NK-1 receptor antagonist (2S,3S)-3-([3,5-bis[trifluoromethyl)phenyl]methoxy)-2-phenylpiperidine (L-733,060) significantly inhibited the inflammatory effects of both toxin A and anandamide. Toxin A increased tissue concentrations of anandamide and 2-AG in the ileum, and these effects were enhanced after pretreatment with inhibitors of fatty acid amide hydrolase, a major endocannabinoid-degrading enzyme. The toxin A-stimulated release of anandamide but not 2-AG was selective over their congeners. These results demonstrate that the endocannabinoids anandamide and 2-AG stimulate intestinal primary sensory neurons via the capsaicin VR1 receptor to release SP, resulting in enteritis, and that endocannabinoids may mediate the inflammatory effects of toxin A.

Address correspondence to: Steven R. Vigna, Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, NC 27710. E-mail: srv{at}duke.edu

This article has been cited by other articles:

				L. Cheng, S. de la Monte, J. Ma, J. Hong, M. Tong, W. Cao, J. Behar, P. Biancani, and K. M. Harnett HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G135 - G143. [Abstract] [Full Text] [PDF]

				Y. S. Lin, R.-L. Lin, M.-Y. Bien, C.-Y. Ho, and Y. R. Kou Sensitization of capsaicin-sensitive lung vagal afferents by anandamide in rats: role of transient receptor potential vanilloid 1 receptors J Appl Physiol, April 1, 2009; 106(4): 1142 - 1152. [Abstract] [Full Text] [PDF]

				D. Wang, H. Wang, W. Ning, M. G. Backlund, S. K. Dey, and R. N. DuBois Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth Cancer Res., August 1, 2008; 68(15): 6468 - 6476. [Abstract] [Full Text] [PDF]

				A A Izzo and M Camilleri Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects Gut, August 1, 2008; 57(8): 1140 - 1155. [Abstract] [Full Text] [PDF]

				V Di Marzo and A A Izzo Endocannabinoid overactivity and intestinal inflammation. Gut, October 1, 2006; 55(10): 1373 - 1376. [Abstract] [Full Text] [PDF]

				F Guagnini, M Valenti, S Mukenge, I Matias, A Bianchetti, S Di Palo, G Ferla, V Di Marzo, and T Croci Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P Gut, July 1, 2006; 55(7): 946 - 953. [Abstract] [Full Text] [PDF]

				K Fujino, S G de la Fuente, Y Takami, T Takahashi, and C R Mantyh Attenuation of acid induced oesophagitis in VR-1 deficient mice Gut, January 1, 2006; 55(1): 34 - 40. [Abstract] [Full Text] [PDF]

				P. Dinis, A. Charrua, A. Avelino, M. Yaqoob, S. Bevan, I. Nagy, and F. Cruz Anandamide-Evoked Activation of Vanilloid Receptor 1 Contributes to the Development of Bladder Hyperreflexia and Nociceptive Transmission to Spinal Dorsal Horn Neurons in Cystitis J. Neurosci., December 15, 2004; 24(50): 11253 - 11263. [Abstract] [Full Text] [PDF]