Inhibition of peristaltic activity by cannabinoids in the isolated distal colon of mouse

Mancinelli, R.; Fabrizi, Adele; Monaco, Serena; Azzena, Gian Battista; Vargiu, Romina; Colombo, Giancarlo; Gessa, Gian Luigi

doi:10.1016/s0024-3205(01)01110-9

Cited by 38 publications

(25 citation statements)

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“…As shown in the present study and by others (15,21,28,29,35), the cannabinoids are potent inhibitors of peristaltic propulsion. This has largely been attributed to inhibition of the ascending contraction component as a result of CB-1 receptormediated inhibition of acetylcholine release.…”

Section: Discussionsupporting

confidence: 86%

“…A similar conclusion was reached by Mancinelli et al (21) using a different CB-1 antagonist SR 141716A, which caused an increase in phasic and tonic activity of murine distal colon. This tonic restraining influence of endocannabinoids would act physiologically to prevent rapid movement of material through the gut, allowing for adequate digestion.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids

Grider¹,

Mahavadi²,

Li³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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This effect has generally been attributed to their ability to prejunctionally inhibit release of acetylcholine from excitatory motor neurons that mediate, in part, the ascending contraction phase of the peristaltic reflex. In the present study we examined the effect of cannabinoids on the other transmitters known to participate in the peristaltic reflex using a three-compartment preparation of rat colon that allows separation of ascending contraction, descending relaxation, and the sensory components of the reflex. On addition to the orad motor compartment, anandamide decreased and AM-251, a CB-1 antagonist, increased ascending contraction and the concomitant substance P (SP) release. Similarly, on addition to the caudad motor compartment, anandamide decreased and AM-251 increased descending relaxation and the concomitant vasoactive intestinal peptide (VIP) release. On addition to the central sensory compartment, anandamide decreased and AM-251 increased both ascending contraction and SP release orad, and descending relaxation and VIP release caudad. This suggested a role for CB-1 receptors in modulation of sensory transmission that was confirmed by the demonstration that central addition of anandamide decreased and AM-251 increased release of the sensory transmitter, calcitonin gene-related peptide (CGRP). We conclude that the potent antipropulsive effect of cannabinoids is the result of inhibition of both excitatory cholinergic/tachykininergic and inhibitory VIPergic motor neurons that mediate ascending contraction and descending relaxation, respectively, as well as inhibition of the intrinsic sensory CGRP-containing neurons that initiate the peristaltic reflex underlying propulsive motility. endocannabinoid; cannabinoid receptors; enteric nervous system; peristalsis; neuropeptides ENDOGENOUS CANNABINOIDS (endocannabinoids) and their receptors are present in the gut tissues where they modulate motility, secretion, and the inflammatory response. Several endocannabinoids are synthesized on demand from fatty acids although the most commonly studied endocannabinoid is anandamide. The endocannabinoids interact mainly with two types of cannabinoid receptors designated CB-1 and CB-2, and in some cases with the TRPV1 (transient receptor potential vanilloid receptor 1 or VR-1) (24,26,36). Recently, studies also suggest that there may be an additional receptor that might mediate some actions of endocannabinoids (6,20,36).Endocannabinoids and the CB-1 and CB-2 receptors are present in the gut although much more is known about the localization of the receptors than the endocannabinoids (9, 16, 28). Both CB-1 and CB-2 receptors are present on enteric neurons that are invariably colocalized with choline acetyltransferase (ChAT) but not vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) (8,10,19,28,29,32). Both Dogiel type I and II enteric neurons have been shown to express CB-1 receptors. The presence of cannabinoid receptors in smooth muscle is controversial although recent evidence suggests the presence of...

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 81%

Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids

Grider¹,

Mahavadi²,

Li³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Other studies also showed that rimonabant, in vitro preparations, enhanced electrically evoked acetylcholine release from myenteric nerves [53] and electrically evoked contractions of myenteric plexus longitudinal muscle obtained from guinea pigs [54, 55]. This excitatory activity is consistent with the ability of rimonabant to increase tonic and phasic activity in isolated mouse colon [56] and increase intestinal motility and defecation in rodents [29, 57]. Prejunctional CB1 receptors were reported to produce inhibition of non-adrenergic non-cholinergic contractile responses in mouse colonic preparations, which was antagonized by rimonabant [58].…”

Section: Rimonabant Gut Motility and Obesitysupporting

confidence: 63%

Rimonabant, Gastrointestinal Motility and Obesity

Sun¹,

Chen²

2012

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Background:Obesity and overweight affect more than half of the US population and are associated with a number of diseases. Rimonabant, a cannabinoid receptor 1 blocker in the endocannabinoid (EC) system, was indicated in Europe for the treatment of obesity and overweight patients with associated risk factors but withdrawn on Jan, 2009 because of side effects. Many studies have reported the effects of rimonabant on gastrointestinal (GI) motility and food intake. The aims of this review are: to review the relationship of EC system with GI motility and food intake;to review the studies of rimonabant on GI motility, food intake and obesity;and to report the tolerance and side effects of rimonabant. Methods:the literature (Pubmed database) was searched using keywords: rimonabant, obesity and GI motility. Results:GI motility is related with appetite, food intake and nutrients absorption. The EC system inhibits GI motility, reduces emesis and increases food intake; Rimonabant accelerates gastric emptying and intestinal transition but decreases energy metabolism and food intake. There is rapid onset of tolerance to the prokinetic effect of rimonabant. The main side effects of rimonabant are depression and GI symptoms. Conclusions:Rimonabant has significant effects on energy metabolism and food intake, probably mediated via its effects on GI motility.

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“…A functional role for endocannabinoids and CB 1 receptors in the gastrointestinal tract is supported by pharmacological studies demonstrating that anandamide and various CB 1 agonists (WIN 55,212-2, CP55,940, and ACEA) but not the CB 2 -selective agonists JWH-133 inhibit gastrointestinal motility in rodents in vivo and in isolated ileum and colon from both experimental animals and humans (Shook and Burks, 1989;Pertwee et al, 1995Pertwee et al, , 1996Coutts and Pertwee, 1997;McCallum et al, 1999;Mancinelli et al, 2001;Mang et al, 2001;Landi et al, 2002;Manara et al, 2002;Hinds et al, 2006). A similar role for endogenous substrates of FAAH is suggested by recent in vivo findings in mice, documenting inhibition of intestinal motility by the FAAH inhibitors N-arachidonoylserotonin and palmitoylisopropylamide and by the FAAH substrates palmitoylethanolamide, oleamide, and oleoylethanolamide in wildtype but not in FAAH knockout mice (Capasso et al, 2005).…”

Section: G Gastrointestinal and Liver Disordersmentioning

confidence: 99%