Fatty acid amide hydrolase controls mouse intestinal motility in vivo.
OBJECTIVE
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.
Capasso
Raffaele
R
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Matias
Isabel
I
Lutz
Beat
B
Borrelli
Francesca
F
Capasso
Francesco
F
Marsicano
Giovanni
G
Mascolo
Nicola
N
Petrosino
Stefania
S
Monory
Krisztina
K
Valenti
Marta
M
Di Marzo
Vincenzo
V
Izzo
Angelo A
AA
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005769:Gastrointestinal Motility / Q000502:physiology*; D005772:Gastrointestinal Transit; D007420:Intestine, Large / Q000502:physiology; D007421:Intestine, Small / Q000502:physiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D012333:RNA, Messenger; D000099252:Fatty Acid Amide Hydrolases