5 years ago

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

l-Ornithine and l-lysine stimulate gastrointestinal motility via transient receptor potential vanilloid 1
Teruo Kawada, Tsuyoshi Goto, Ryo Omae, Junya Nakato, Kousaku Ohinata, Takafumi Mizushige, Yee Yin Ho, Ryuhei Kanamoto, Minji Kim, Saori Akiduki, Nobuyuki Takahashi, Makoto Tominaga, Kunitoshi Uchida
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 NG-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. Among basic amino acids, l-ornithine (Orn) and l-lysine (Lys) stimulated but l-arginine (Arg) suppressed gastrointestinal (GI) motility after oral administration. Orn- and Lys-induced GI motility stimulation was inhibited by either TRPV1 antagonist or TRPV1-knockout mice. The stimulatory effect of Orn and Lys on GI motility was also mediated by muscarinic acetylcholine receptor and nitric oxide synthase.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201700230

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