Endocannabinoids as physiological regulators of colonic propulsion in mice

Pinto, Luísa; Izzo, Angelo A.; Cascio, Maria Grazia; Bisogno, Tiziana; Hospodar-Scott, Karen; Brown, David R.; Mascolo, Nicola; Marzo, Vincenzo Di; Capasso, Francesco

doi:10.1053/gast.2002.34242

Cited by 169 publications

(179 citation statements)

References 40 publications

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“…For example they inhibit GI transit and motility in rats (Landi et al, 2002), decrease the intragastric pressure and the pyloric contractility by activating CB 1 receptors (Krowicki et al, 1999), tonically inhibit colonic propulsion (Pinto et al, 2002) and decrease GI transit in mice (Izzo et al, 2000). CB 1 receptor agonists decreased the gastric acid secretion induced by pentagastrin given intravenously (Adami et al, 2002), but i.c.v.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Gyires

Rónai

Zádori

et al. 2014

Molecular and Cellular Endocrinology

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The aim of the present study was to analyze whether angiotensin II via the endocannabinoid system can induce gastric mucosal protection, since transactivation of cannabinoid CB1 receptors by angiotensin AT1 receptor in CHO cells was described. Experimental ulcer was induced by acidified ethanol given orally in male Wistar rats, CB1(+/+) wild type and CB1(-/-) knock out mice. The compounds were administered intracerebroventricularly. It was found, that 1./ Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191 pmol); the effect of angiotensin II (191 pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8 nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2 nmol). 2./ Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3./ The gastroprotective effect of angiotensin II (191 pmol) was reduced by atropine (1 mg/kg i.v.) and bilateral cervical vagotomy. In conclusion, stimulation of central angiotensin AT1 receptors via activation of cannabinoid CB1 receptors induces gastroprotection in a DAGL-dependent and vagus-mediated mechanism.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Gyires

Rónai

Zádori

et al. 2014

Molecular and Cellular Endocrinology

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“…Studies of the physiological role of cannabinoids in the gastrointestinal tract are becoming increasingly important because of the finding that endocannabinoids are present in the gut (32). Endocannabinoids have been shown to be physiological regulators of gastrointestinal motor functions (27,33), but their role in the modulation of intestinal secretion under normal conditions has not been extensively investigated. However, there are recent data to show that an endogenous cannabinoid tone is important in regulating the extent of the secretory response to cholera toxin (20).…”

Section: Discussionmentioning

confidence: 99%

Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves

MacNaughton

Sickle²,

Keenan³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves. Am J Physiol Gastrointest Liver Physiol 286: G863-G871, 2004. First published December 30, 2003 10.1152/ ajpgi.00482.2003.-We investigated the distribution and function of cannabinoid (CB)1 receptors in the submucosal plexus of the guinea pig ileum. CB 1 receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB1 receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB1 receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current (I sc) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I sc responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, ␣-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-D-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 Ϯ 12 and 30 Ϯ 14%, respectively, by the CB1 receptor agonist WIN 55,212-2. This inhibitory effect was blocked by the CB 1 receptor antagonist, SR 141716A. I sc responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212-2. The inhibitory effect of WIN 55,212-2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB1 receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways. submucosal plexus; vasoactive intestinal peptide; neuropeptide Y; transient receptor potential vanilloid-1 receptor THE ENTERIC NERVOUS SYSTEM exerts tight control over electrolyte and water transport by the intestinal epithelium (5, 7). Specifically, submucosal secretomotor neurons release vasoactive intestinal polypeptide and acetylcholine to activate cAMP-or Ca 2ϩ -dependent pathways, respectively, which control the gating of chloride transport through apically situated chloride transporters in enterocytes. The apically directed transport of chloride occurs predominantly via the cystic fibrosis transmembrane conductance regulator or a member of the calciumdependent chloride channel family (4). Whereas the intrinsic properties of these transporters have been, and continue to be, the subject of numerous studies, less well documented are the inputs that control the a...

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Section: Role Of the Ecs In Gut Homeostasismentioning

confidence: 99%

“…Cannabinoids and endocannabinoid degradation inhibitors decrease intestinal motility, peristalsis, and colonic propulsion in rodents, primarily in a CB 1 -dependent manner [7][8][9][10][11][12]. Accordingly, [8,9,13,14]. It is likely that cannabinoids inhibit contractility by reducing acetylcholine release from enteric nerves because they do not inhibit contractions produced by exogenous administration of acetylcholine but reduce electrically-evoked acetylcholine release from myenteric nerves [7,15,16].…”

Section: Role Of the Ecs In Gut Homeostasismentioning

confidence: 99%

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

Alhouayek

Muccioli

2012

Trends in Molecular Medicine

119

100

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Endocannabinoids as physiological regulators of colonic propulsion in mice

Cited by 169 publications

References 40 publications

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

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