title: An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice.
abstract: OBJECTIVE
  Cholera toxin (CT) is the most recognizable enterotoxin causing secretory diarrhea, a major cause of infant morbidity and mortality throughout the world. In this study, we investigated the role of the endogenous cannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) in CT-induced fluid accumulation in the mouse small intestine.
  
  
  METHODS
  Fluid accumulation was evaluated by enteropooling; endocannabinoid levels were measured by isotope-dilution gas chromatography mass spectrometry; CB(1) receptors were localized by immunohistochemistry and their messenger RNA (mRNA) levels were quantified by reverse-transcription polymerase chain reaction (PCR).
  
  
  RESULTS
  Oral administration of CT to mice resulted in an increase in fluid accumulation in the small intestine and in increased levels of the endogenous cannabinoid, anandamide, and increased expression of the cannabinoid CB(1) receptor mRNA. The cannabinoid receptor agonist CP55,940 and the selective cannabinoid CB(1) receptor agonist arachidonoyl-chloro-ethanolamide inhibited CT-induced fluid accumulation, and this effect was counteracted by the CB(1) receptor antagonist SR141716A, but not by the CB(2) receptor antagonist SR144528. SR141716A, per se, but not the vanilloid VR1 receptor antagonist capsazepine, enhanced fluid accumulation induced by CT, whereas the selective inhibitor of anandamide cellular uptake, VDM11, prevented CT-induced fluid accumulation.
  
  
  CONCLUSIONS
  These results indicate that CT, along with enhanced intestinal secretion, causes overstimulation of endocannabinoid signaling with an antisecretory role in the small intestine.
authors.affiliation: Department of Experimental Pharmacology, University of Naples, "Frederico II", Naples, Italy. aaizzo@unina.it
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Capasso
authors.forename: Anna
authors.initials: A
authors.lastname: Costagliola
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Alessia
authors.initials: A
authors.lastname: Ligresti
authors.forename: Isabel
authors.initials: I
authors.lastname: Matias
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.forename: Luisa
authors.initials: L
authors.lastname: Pinto
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Cecio
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Nicola
authors.initials: N
authors.lastname: Mascolo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000032:analysis; D000818:Animals; D063385:Cannabinoid Receptor Modulators; D002714:Chlorisondamine / Q000494:pharmacology; D002772:Cholera Toxin / Q000633:toxicity*; D063388:Endocannabinoids; D004983:Ethanolamines; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000502:physiology*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010169:Palmitic Acids / Q000032:analysis; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D002714:Chlorisondamine; D002772:Cholera Toxin; D063388:Endocannabinoids; D004983:Ethanolamines; D005231:Fatty Acids, Unsaturated; D010169:Palmitic Acids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000099252:Fatty Acid Amide Hydrolases; C005958:palmidrol