Abstract
Cannabidiol (CBD) has been shown to inhibit gastrointestinal (GI) transit in pathophysiologic in vivo models, while having no effect in physiologic controls. The actions of the precursor of CBD, cannabidiolic acid (CBDA), have not been investigated in the GI tract. The actions of these phytocannabinoids on the contractility of the GI tract of Suncus murinus were investigated in the current study. The effects of CBDA and CBD in resting state and pre-contracted isolated intestinal segments, and on the contractile effects of carbachol and electrical field stimulation (EFS) on the intestines of S. murinus were examined. CBDA and CBD induced a reduction in resting tissue tension of isolated intestinal segments which was not blocked by the cannabinoid CB1 receptor antagonist, AM251, the CB2 receptor antagonist AM630, or tetrodotoxin. CBDA and CBD reduced the magnitude of contractions induced by carbachol and the tension of intestinal segments that were pre-contracted with potassium chloride. In tissues stimulated by EFS, CBDA inhibited contractions induced by lower frequencies (0.1–4.0 Hz) of EFS, while CBD inhibited contractions induced by higher frequencies (4.0–20.0 Hz) of EFS. The data suggest that CBDA and CBD have inhibitory actions on the intestines of S. murinus that are not neuronallymediated or mediated via CB1 or CB2 receptors.
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References
Adams, R., Hunt, M., and Clark, J. H., Structure of cannabidiol, a product isolated from the marihuana extract of Minnesota wild hemp I. J. Am. Chem. Soc., 62, 196–200 (1940).
Bisogno, T., Hanus, L., De Petrocellis L., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., and Di Marzo, V., Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol., 134, 845–852 (2001).
Bolton, T. B., Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev., 59, 606–718 (1979).
Borrelli, F., Aviello, G., Romano, B., Orlando, P., Capasso, R., Maiello, F., Guadagno, F., Petrosino, S., Capasso, F., Di Marzo, V., and Izzo, A. A., Cannabidiol, a safe and nonpsychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis. J. Mol. Med (Berl)., 87, 1111–1121 (2009).
Capasso, R., Borrelli, F., Aviello, G., Romano, B., Scalisi, C., Capasso, F., and Izzo, A. A., Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br. J. Pharmacol., 154, 1001–1008 (2008).
Colbert, E. H., Evolution of vertebrates, 2nd ed. Wiley & sons, New York, (1969).
de Filippis, D., Iuvone, T., d’amico, A., Esposito, G., Steardo, L., Herman, A. G., Pelckmans, P. A., de Winter, B. Y., and de Man, J. G., Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB receptors and fatty acid amide hydrolase. Neurogastroenterol. Motil., 20, 919–927 (2008).
de Man, J. G., Boeckx, S., Anguille, S., de Winter, B. Y., de Schepper, H. U., Herman, A. G., and Pelckmans, P. A., Functional study on TRPV1-mediated signalling in the mouse small intestine: involvement of tachykinin receptors. Neurogastroenterol. Motil., 20, 546–556 (2008).
de Zeeuw, R. A., Wijsbeek, J., Breimer, D. D., Vree, T. B., van Ginneken, C. A., and van Rossum, J. M., Cannabinoids with a propyl side-chain in cannabis: occurrence and chromatographic behavior. Science, 175, 778–779 (1972).
Drysdale, A. J., Ryan, D., Pertwee, R. G., and Platt, B., Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells. Neuropharmacology, 50, 621–631 (2006).
el-Darawy, Z. I., Abu-Eitah, R., and Mobarak, Z. M., Studies on hashish. 5-Identification of cannabidiol and cannabidiolic acid by ultraviolet spectrophotometry. Pharmazie, 28, 129–133 (1973).
Fujimoto, S., Mori, M., Tsushima, H., and Kunimatsu, M., Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum. Eur. J. Pharmacol., 530, 144–151 (2006).
Gershon, M. D., Effects of tetrodotoxin on innervated smooth muscle preparations. Br. J. Pharmacol. Chemother., 29, 259–279 (1967).
Harada, N., Nemoto, K., Okamura, T., Ninomiya, N., Suzuki, H., and Yamamoto, Y., Effects of cannabinoids on colonic muscle contractility and tension in guinea pigs. J. Nihon Med. Sch., 72, 43–51 (2005).
Hoyle, C. H., Chakrabarti, G., Pendleton, N. P., and Andrews, P. L., Neuromuscular transmission and innervation in the urinary bladder of the insectivore Suncus murinus. J. Auton. Nerv. Syst., 69, 31–38 (1998).
Hoyle, C. H., Hill, J., Sanger, G. J., and Andrews, P. L., Analysis of pancreatic polypeptide cDNA from the house musk shrew, Suncus murinus, suggests a phylogenetically closer relationship with humans than for other small laboratory animal species. Regul. Pept., 114, 137–144 (2003).
Jacob, A. and Todd, A. R., Cannabis indica part II isolation of cannabidiol from Egyptian hashish observations on the structure of cannabinol. J. Chem. Soc., 649–653 (1940).
Javid, F. A. and Naylor, R. J., Characterisation of 5-HT2 receptor subtypes in the Suncus murinus intestine. Eur. J. Pharmacol., 381, 161–169 (1999a).
Javid, F. A. and Naylor, R. J., Characterization of the 5-hydroxytryptamine receptors mediating contraction in the intestine of Suncus murinus. Br. J. Pharmacol., 127, 1867–1875 (1999b).
Kao, C. Y., Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol. Rev., 18, 997–1049 (1966).
Krejci, K. D. and Santavy, F., Isolace dalsich latek z listi indickeho konopi Cannabis sativa L. Acta Univ. Palacki. Olomuc. Fac. Med., 6, 59–66 (1955).
Kurohmaru, M., Nishida, T., and Mochizuki, K., Morphological study on the intestine of the must shrew, Suncus murinus. Nihon Juigaku Zasshi, 42, 61–71 (1980).
Mechoulam, R. and Gaoni, Y., Hashish, IV. The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids. Tetrahedron, 21, 1223–1229 (1965).
Russo, E., History of cannabis as a medicine, in The medicinal uses of cannabis and cannabinioids, Guy, G. W., Whittle, B. A., and Robson, P. J. (eds.). Pharmaceutical Press, London, pp. 1–15, (2003).
Showalter, V. M., Compton, D. R., Martin, B. R., and Abood, M. E., Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J. Pharmacol. Exp. Ther., 278, 989–999 (1996).
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Cluny, N.L., Naylor, R.J., Whittle, B.A. et al. The effects of cannabidiolic acid and cannabidiol on contractility of the gastrointestinal tract of Suncus murinus . Arch. Pharm. Res. 34, 1509–1517 (2011). https://doi.org/10.1007/s12272-011-0913-6
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DOI: https://doi.org/10.1007/s12272-011-0913-6