An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice
Gastroenterology. 2003-09-01; 125(3): 765-774
DOI: 10.1016/S0016-5085(03)00892-8
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1. Gastroenterology. 2003 Sep;125(3):765-74. doi: 10.1016/s0016-5085(03)00892-8.
An endogenous cannabinoid tone attenuates cholera toxin-induced fluid
accumulation in mice.
Izzo AA(1), Capasso F, Costagliola A, Bisogno T, Marsicano G, Ligresti A, Matias
I, Capasso R, Pinto L, Borrelli F, Cecio A, Lutz B, Mascolo N, Di Marzo V.
Author information:
(1)Department of Experimental Pharmacology, University of Naples, “Frederico
II”, Naples, Italy.
Comment in
Gastroenterology. 2003 Sep;125(3):973-5.
BACKGROUND & AIMS: 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.
DOI: 10.1016/s0016-5085(03)00892-8
PMID: 12949722 [Indexed for MEDLINE]