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Endocannabinoids and the gastrointestinal tract: what are the key questions?
Author(s) -
Sanger G J
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707422
Subject(s) - endocannabinoid system , trpv1 , cannabinoid receptor , cannabinoid receptor type 2 , gastric emptying , receptor , cannabinoid , medicine , endocrinology , agonist , stomach , transient receptor potential channel
Cannabinoid (CB 1 ) receptor activation acts neuronally, reducing GI motility, diarrhoea, pain, transient lower oesophageal sphincter relaxations (TLESRs) and emesis, and promoting eating. CB 2 receptor activation acts mostly via immune cells to reduce inflammation. What are the key questions which now need answering to further understand endocannabinoid pathophysiology? GPR55. Does this receptor have a GI role? Satiety, Nausea, Vomiting, Gastro‐Oesophageal Reflux, Gastric Emptying. Endocannabinoids acting at CB 1 receptors can increase food intake and body weight, exert anti‐emetic activity, reduce gastric acid secretion and TLESRs; CB 2 receptors may have a small role in emesis. Question 1: CB 1 receptor activation reduces emesis and gastric emptying but the latter is associated with nausea. How is the paradox explained? Q2: Do non‐CB receptor actions of endocannabinoids (for example TRPV1) also modulate emesis? Q3: Is pathology necessary (gastritis, gastro‐oesophageal reflux) to observe CB 2 receptor function? Intestinal Transit and Secretion. Reduced by endocannabinoids at CB 1 receptors, but not by CB 2 receptor agonists. Q1: Do the effects of endocannabinoids rapidly diminish with repeat‐dosing? Q2: Do CB 2 receptors need to be pathologically upregulated before they are active? Inflammation. CB 1 , CB 2 and TRPV1 receptors may mediate an ability of endocannabinoids to reduce GI inflammation or its consequences. Q1: Are CB 2 receptors upregulated by inflammatory or other pathology? Pain. Colonic bacterial flora may upregulate CB 2 receptor expression and thereby increase intestinal sensitivity to noxious stimuli. Q1: Are CB 2 receptors the interface between colonic bacteria and enteric‐ or extrinsic nerve sensitivity? Relevance of endocannabinoids to humans. Perhaps apart from appetite, this is largely unknown. British Journal of Pharmacology (2007) 152 , 663–670. doi: 10.1038/sj.bjp.0707422 ; published online 3 September 2007