An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice

Izzo, Angelo A.; Capasso, Francesco; Costagliola, Anna; Bisogno, Tiziana; Marsicano, Giovanni; Ligresti, Alessia; Matias, Isabel; Capasso, Raffaele; Pinto, Luísa; Borrelli, Francesca; Cecio, A; Lutz, Beat; Mascolo, Nicola; Marzo, Vincenzo Di

doi:10.1016/s0016-5085(03)00892-8

Cited by 123 publications

(92 citation statements)

References 51 publications

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“…This requires further electrophysiological investigations. CB 1 receptors have been described previously in the porcine and murine submucosal plexus (20,23) as they have in the myenteric plexus (9). In the pig, CB 1 receptor immunoreactivity was found colocalized with cholineacetyltransferase and substance P (23), which is consistent with observations we have made.…”

Section: Discussionsupporting

confidence: 91%

“…In the pig, CB 1 receptor immunoreactivity was found colocalized with cholineacetyltransferase and substance P (23), which is consistent with observations we have made. It was similarly colocalized in the mouse (20). In the pig, it was not found in VIP neurons, which is different from the guinea pig (23).…”

Section: Discussionmentioning

confidence: 72%

“…Interestingly, VIP receptor desensitization did not affect the I sc response to capsaicin. Similarly, experiments with the VIP receptor antagonists VIP [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] (16) (14) did not affect the response to capsaicin. Indeed, in our preparations, these antagonists failed even to block the secretory response to serosally applied VIP (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…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). This suggests that CB 1 receptors may have important roles in pathophysiological conditions in the gut and that drugs interfering with endocannabinoid metabolism may be useful therapeutically in a variety of diseases of the gastrointestinal tract (10).…”

Section: Discussionmentioning

confidence: 99%

“…These studies have recently been extended to show that endogenous cannabinoids play a role in the regulation of fluid secretion. Experiments in mouse have shown that upregulated expression of CB 1 receptors on enteric nerves is responsible for the protective actions of anandamide in cholera toxin-induced fluid secretion in vivo (20).…”

mentioning

confidence: 99%

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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

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: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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

MacNaughton

Sickle²,

Keenan³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Potential therapeutic applications of cannabinoids in gastrointestinal and liver diseases: Focus on Δ9‐tetrahydrocannabinol pharmacology

et al. 2014

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Physiological roles of 2‐arachidonoylglycerol, an endogenous cannabinoid receptor ligand

2009

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2-Arachidonoylglycerol is an arachidonic acid-containing monoacylglycerol isolated from the rat brain and canine gut as an endogenous ligand for the cannabinoid receptors (CB1 and CB2). 2-Arachidonoylglycerol binds to both the CB1 receptor, abundantly expressed in the nervous system, and the CB2 receptor, mainly expressed in the immune system, with high affinity, and exhibits a variety of cannabimimetic activities. Notably, anandamide, another endogenous ligand for the cannabinoid receptors, acts as a partial agonist at these cannabinoid receptors, whereas 2-arachidonoylglycerol acts as a full agonist. The results of structure-activity relationship experiments strongly suggested that 2-arachidonoylglycerol rather than anandamide is the true natural ligand for both the CB1 and the CB2 receptors. Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays physiologically and pathophysiologically essential roles in various mammalian tissues and cells.

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An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice

Cited by 123 publications

References 51 publications

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

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

Potential therapeutic applications of cannabinoids in gastrointestinal and liver diseases: Focus on Δ9‐tetrahydrocannabinol pharmacology

Physiological roles of 2‐arachidonoylglycerol, an endogenous cannabinoid receptor ligand

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