Fatty acid amide hydrolase controls mouse intestinal motility in vivo.
Gastroenterology. 2005-09-01; 129(3): 941-951
DOI: 10.1053/j.gastro.2005.06.018
Read on PubMed
1. Gastroenterology. 2005 Sep;129(3):941-51.
Fatty acid amide hydrolase controls mouse intestinal motility in vivo.
Capasso R(1), Matias I, Lutz B, Borrelli F, Capasso F, Marsicano G, Mascolo N,
Petrosino S, Monory K, Valenti M, Di Marzo V, Izzo AA.
Author information:
(1)Department of Experimental Pharmacology, University of Naples Federico II,
Naples, Italy.
BACKGROUND & AIMS: Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis
both of the endocannabinoids (which are known to inhibit intestinal motility) and
other bioactive amides (palmitoylethanolamide, oleamide, and oleoylethanolamide),
which might affect intestinal motility. The physiologic role of FAAH in the gut
is largely unexplored. In the present study, we evaluated the possible role of
FAAH in regulating intestinal motility in mice in vivo.
METHODS: Motility was measured by evaluating the distribution of a fluorescent
marker along the small intestine; FAAH messenger RNA (mRNA) levels were analyzed
by reverse-transcription polymerase chain reaction (RT-PCR); endocannabinoid
levels were measured by isotope-dilution, liquid chromatography, mass
spectrometry.
RESULTS: Motility was inhibited by N-arachidonoylserotonin (AA-5-HT) and
palmitoylisopropylamide, 2 selective FAAH inhibitors, as well as by the FAAH
substrates palmitoylethanolamide, oleamide, and oleoylethanolamide. The effect of
AA-5-HT was reduced by the CB1 receptor antagonist rimonabant and by CB1
deficiency in mice but not by the vanilloid receptor antagonist
5′-iodoresiniferatoxin. In FAAH-deficient mice, pharmacologic blockade of FAAH
did not affect intestinal motility. FAAH mRNA was detected in different regions
of the intestinal tract.
CONCLUSIONS: We conclude that FAAH is a physiologic regulator of intestinal
motility and a potential target for the development of drugs capable of reducing
intestinal motility.
DOI: 10.1053/j.gastro.2005.06.018
PMID: 16143133 [Indexed for MEDLINE]