L-Ornithine and L-lysine stimulate gastrointestinal motility via transient receptor potential vanilloid 1.

Scope: The gastrointestinal (GI) tract senses and responds to intraluminal nutrients and these interactions often affect GI functions. We found that, among basic amino acids, L-ornithine (Orn) and L-lysine (Lys) stimulated but L-arginine (Arg) suppressed GI motility after oral administration (24 mmol/kg) in mice (Orn and Lys, 14.3 and 26.4% promotion; Arg, 7.7% suppression). We investigated the mechanism of the action of Orn and Lys on GI motility. Methods and results: Orn-induced promotion of small intestinal transit was significantly inhibited (p<0.05) by oral administration of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. Moreover, the stimulatory effect of Orn and Lys was abolished in TRPV1-knockout mice. In TRPV1-transfected HEK293 cells, Orn and Lys (10 mM) evoked Ca2+ influx, which was blocked by ruthenium red, a TRP channel antagonist. These results suggest that Orn and Lys promote GI motility via activation of TRPV1. The GI motility stimulation by Orn and Lys was also blocked by atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, or N-G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor. Conclusion; Orally administered Orn and Lys stimulate GI motility via TRPV1, mAChR and NO synthase in mice.