Effects of Cannabinoids on Colonic Muscle Contractility and Tension in Guinea Pigs
Objective: While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro. Design: Prospective...
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| Published in | Journal of Nippon Medical School Vol. 72; no. 1; pp. 43 - 51 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan
The Medical Association of Nippon Medical School
2005
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1345-4676 1347-3409 |
| DOI | 10.1272/jnms.72.43 |
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| Abstract | Objective: While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro. Design: Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist. Setting: University research laboratory Subjects: Thirty guinea pigs (20 for in vivo study, 10 for in vitro) Measurements and main results: Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca2+-activated K+-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension. Conclusions: Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression. |
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| AbstractList | Objective： While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro. Design： Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2;a cannabinoid antagonist, AM281;and ion-channel antagonist. Setting： University research laboratory Subjects： Thirty guinea pigs (20 for in vivo study, 10 for in vitro) Measurements and main results： Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca2+ -activated K+ -channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension. Conclusions： Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression. (J Nippon Med Sch 2005;72：43-51) While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro.OBJECTIVEWhile endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro.Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist.DESIGNProspective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist.University research laboratory.SETTINGUniversity research laboratory.Thirty guinea pigs (20 for in vivo study, 10 for in vitro).SUBJECTSThirty guinea pigs (20 for in vivo study, 10 for in vitro).Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca(2+)-activated K(+)-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension.MEASUREMENTS AND MAIN RESULTSColonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca(2+)-activated K(+)-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension.Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression.CONCLUSIONSCannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression. Objective: While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro. Design: Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist. Setting: University research laboratory Subjects: Thirty guinea pigs (20 for in vivo study, 10 for in vitro) Measurements and main results: Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca2+-activated K+-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension. Conclusions: Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression. While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro. Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist. University research laboratory. Thirty guinea pigs (20 for in vivo study, 10 for in vitro). Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca(2+)-activated K(+)-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension. Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression. |
| Author | Ninomiya, Norifumi Suzuki, Hidenori Harada, Naoshige Okamura, Tadao Yamamoto, Yasuhiro Nemoto, Kayo |
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| Cites_doi | 10.1038/sj.bjp.0701393 10.3893/jjaam.11.651 10.1097/00075198-200204000-00011 10.1038/sj.bjp.0701301 10.1038/sj.bjp.0701964 10.1073/pnas.96.24.14136 10.1053/gast.2002.34242 10.1038/sj.bjp.0701361 10.1152/ajpgi.00148.2003 10.1111/j.1476-5381.1996.tb15663.x 10.1124/jpet.301.3.963 10.1074/jbc.M307258200 10.1016/S0014-2999(03)01813-2 10.1006/abio.2001.5015 10.3893/jjaam.14.241 |
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| References | 6) Pinto L, Izzo AA, Cascio MG, Bisogno T, Hospodar-Scott K, Brown DR, Mascolo N, DI Marzo V, Caposso F. Endocannabinoids as physiological regulators of colonoc propulsion in mice. Gastroenterology 2002; 123: 227-234. 15) Ralevic V. Cannabinoid modulation of peripheral autonomic and sensory neurotransmission. Euro J of pharmacol 2003; 472: 1-21. 1) Marik PE, Varon J: Sepsis: Intensive care medicine (Irwin RS, Rippe JM, eds), Fifth Edition, 2003; pp1822-1833, Lippincott Williams & Wilkins, Philadelphia. 16) Rawls SM, Cabassa J, Geller EB, Adler MW. CB1 receptor in the preoptic anterior hypothalamus regulate WIN55212-2 [ (4, 5-dihydro-2-methyl-4-(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo [3, 2, 1ij] quinolin-6-one)-induced hypothermia. J Pharmacol Exp Ther 2002; 301: 963-968. 2) Bauer AJ, Schwartz NT, Moore BA, Turler A, Kalff JC. Ileus in critical illness: mechanisms and management. Current Opinion in Critical Care 2002; 8: 152-158. 3) Wang Y, Liu Y, Ito Y, Hashiguchi T, Kitajima I, Yamaguchi M, Shimizu H, Matsuo S, Imaizumi H, Marukawa I. Simultaneous measurement of anandamide and arachidonoylglycerol by polimyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: Increase in endogenous cannabinoids in the sera of patients with end toxic shock. Analytical Biochemistry 2001; 294: 73-82. 4) Coutts AA, Pertwee RG. Inhibition by cannabinoid receptor agonists of acetylcholine release from the guinea-pig myenteric plexus. Br J Pharmacol 1997; 121: 1557-1566. 11) Pertwee RG, Fernand SR, Nash JE, Coutts AA. Further evidence for the presence of cannabinoid CB1 recepters in guina-pig small intestine. Br J Pharmacol 1996; 118: 2199-2205. 14) Plane F, Holland M, Walderon GJ, Garland CJ, Boyle JP. Evidence that anandamide and EDHF act via different mechanisms in rat isolated mesenteric arteries. Br J Pharmacol 1997; 121: 1509-1511. 8) Ninomiya N, Nemoto K, Okamura T, Suzuki H, Yamamoto Y. A novel experimental method for the study of intestinal paralysis due to endotoxicosis. J Jap Assoc Acute Med 2003; 14: 241-250. 13) Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR, Zimmer AM, Bonner TI, Buckley NE, Mezey E, Razdan RK, Zimmer A, Kunos G. Cannabinoid-induced mesenteric vasodilatation through an endothelial site distinct from CB1 or CB2 receptor. Proc Natl Acad Sci 1999; 96: 14136-14141. 12) Begg M, Mo FM, Offertáler L, Bátkai S, Pacher P, Razdan RK, Lovinger DM, Kunos G. G Protein-coupled endthelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+current. J of biol chemistry 2003; 278: 46188-46194. 9) Storr M, Sibaev A, Marsciano G, Lutz B, Schusdziarra V, Timmermans JP, Allescher HD. Cannabinoid recepter type 1 modulates exciatory and inhibitory neurotransmission in mouse colon. AJP Gastrointest Liver Physiol 2004; 286: 110-117. 10) Lopez-Redondo F, Lees, GM, Pertwee RG. Effects of cannabinoid receptor ligands on electrophysiological properties of myenteric neurones of the guinea-pig ileum. Br J Pharmacol 1997; 122: 330-384. 5) Izzo AA, Mascolo N, Borrelli F, Capasso F. Excitatory transmission to the circular muscle of the guinea-pig ileum: Evidence for the involvement of cannabinoid CB1 receptor. Br J Pharmacol 1998; 124: 1363-1368. 7) Ninomiya N, Nemoto K, Okamura T, Yamamoto Y. Suppression of guinea pig intestinal tract contraction by lipopolysaccharide. J Jap Assoc Acute Med 2000; 11: 651-659. 11 12 13 14 15 16 1 2 4 5 6 7 8 9 (3) 2001; 294 10 |
| References_xml | – reference: 14) Plane F, Holland M, Walderon GJ, Garland CJ, Boyle JP. Evidence that anandamide and EDHF act via different mechanisms in rat isolated mesenteric arteries. Br J Pharmacol 1997; 121: 1509-1511. – reference: 1) Marik PE, Varon J: Sepsis: Intensive care medicine (Irwin RS, Rippe JM, eds), Fifth Edition, 2003; pp1822-1833, Lippincott Williams & Wilkins, Philadelphia. – reference: 2) Bauer AJ, Schwartz NT, Moore BA, Turler A, Kalff JC. Ileus in critical illness: mechanisms and management. Current Opinion in Critical Care 2002; 8: 152-158. – reference: 6) Pinto L, Izzo AA, Cascio MG, Bisogno T, Hospodar-Scott K, Brown DR, Mascolo N, DI Marzo V, Caposso F. Endocannabinoids as physiological regulators of colonoc propulsion in mice. Gastroenterology 2002; 123: 227-234. – reference: 16) Rawls SM, Cabassa J, Geller EB, Adler MW. CB1 receptor in the preoptic anterior hypothalamus regulate WIN55212-2 [ (4, 5-dihydro-2-methyl-4-(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo [3, 2, 1ij] quinolin-6-one)-induced hypothermia. J Pharmacol Exp Ther 2002; 301: 963-968. – reference: 9) Storr M, Sibaev A, Marsciano G, Lutz B, Schusdziarra V, Timmermans JP, Allescher HD. Cannabinoid recepter type 1 modulates exciatory and inhibitory neurotransmission in mouse colon. AJP Gastrointest Liver Physiol 2004; 286: 110-117. – reference: 15) Ralevic V. Cannabinoid modulation of peripheral autonomic and sensory neurotransmission. Euro J of pharmacol 2003; 472: 1-21. – reference: 3) Wang Y, Liu Y, Ito Y, Hashiguchi T, Kitajima I, Yamaguchi M, Shimizu H, Matsuo S, Imaizumi H, Marukawa I. Simultaneous measurement of anandamide and arachidonoylglycerol by polimyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: Increase in endogenous cannabinoids in the sera of patients with end toxic shock. Analytical Biochemistry 2001; 294: 73-82. – reference: 4) Coutts AA, Pertwee RG. Inhibition by cannabinoid receptor agonists of acetylcholine release from the guinea-pig myenteric plexus. Br J Pharmacol 1997; 121: 1557-1566. – reference: 7) Ninomiya N, Nemoto K, Okamura T, Yamamoto Y. Suppression of guinea pig intestinal tract contraction by lipopolysaccharide. J Jap Assoc Acute Med 2000; 11: 651-659. – reference: 13) Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR, Zimmer AM, Bonner TI, Buckley NE, Mezey E, Razdan RK, Zimmer A, Kunos G. Cannabinoid-induced mesenteric vasodilatation through an endothelial site distinct from CB1 or CB2 receptor. Proc Natl Acad Sci 1999; 96: 14136-14141. – reference: 8) Ninomiya N, Nemoto K, Okamura T, Suzuki H, Yamamoto Y. A novel experimental method for the study of intestinal paralysis due to endotoxicosis. J Jap Assoc Acute Med 2003; 14: 241-250. – reference: 10) Lopez-Redondo F, Lees, GM, Pertwee RG. Effects of cannabinoid receptor ligands on electrophysiological properties of myenteric neurones of the guinea-pig ileum. Br J Pharmacol 1997; 122: 330-384. – reference: 5) Izzo AA, Mascolo N, Borrelli F, Capasso F. Excitatory transmission to the circular muscle of the guinea-pig ileum: Evidence for the involvement of cannabinoid CB1 receptor. Br J Pharmacol 1998; 124: 1363-1368. – reference: 11) Pertwee RG, Fernand SR, Nash JE, Coutts AA. Further evidence for the presence of cannabinoid CB1 recepters in guina-pig small intestine. Br J Pharmacol 1996; 118: 2199-2205. – reference: 12) Begg M, Mo FM, Offertáler L, Bátkai S, Pacher P, Razdan RK, Lovinger DM, Kunos G. G Protein-coupled endthelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+current. J of biol chemistry 2003; 278: 46188-46194. – ident: 10 doi: 10.1038/sj.bjp.0701393 – ident: 7 doi: 10.3893/jjaam.11.651 – ident: 1 – ident: 2 doi: 10.1097/00075198-200204000-00011 – ident: 4 doi: 10.1038/sj.bjp.0701301 – ident: 5 doi: 10.1038/sj.bjp.0701964 – ident: 13 doi: 10.1073/pnas.96.24.14136 – ident: 6 doi: 10.1053/gast.2002.34242 – ident: 14 doi: 10.1038/sj.bjp.0701361 – ident: 9 doi: 10.1152/ajpgi.00148.2003 – ident: 11 doi: 10.1111/j.1476-5381.1996.tb15663.x – ident: 16 doi: 10.1124/jpet.301.3.963 – ident: 12 doi: 10.1074/jbc.M307258200 – ident: 15 doi: 10.1016/S0014-2999(03)01813-2 – volume: 294 start-page: 73 issn: 0003-2697 year: 2001 ident: 3 publication-title: Analytical Biochemistry doi: 10.1006/abio.2001.5015 – ident: 8 doi: 10.3893/jjaam.14.241 |
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| Snippet | Objective: While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded... Objective： While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded... While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility... |
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| SubjectTerms | Animals Arachidonic Acids - pharmacology Benzoxazines Body Temperature - drug effects Cannabinoid Receptor Modulators - pharmacology cannabinoids Cannabinoids - agonists CB1 recepter colon Colon - drug effects contractility Electric Stimulation Endocannabinoids Gastrointestinal Motility - drug effects Glycerides - pharmacology guinea pig Guinea Pigs In Vitro Techniques Male Morpholines - pharmacology Muscle Contraction - drug effects Naphthalenes - pharmacology Pyrazoles - pharmacology Receptor, Cannabinoid, CB1 - antagonists & inhibitors Receptor, Cannabinoid, CB1 - physiology tension |
| Title | Effects of Cannabinoids on Colonic Muscle Contractility and Tension in Guinea Pigs |
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