RESUMO
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.
Assuntos
Sinalização do Cálcio , Motilidade Gastrointestinal , Lisina/administração & dosagem , Ornitina/administração & dosagem , Canais de Cátion TRPV/agonistas , Regulação para Cima , Animais , Arginina/administração & dosagem , Arginina/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Células HEK293 , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Lisina/metabolismo , Masculino , Moduladores de Transporte de Membrana/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Ornitina/metabolismo , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Rutênio Vermelho/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
We found that intraduodenal administration of l-ornithine (l-Orn) stimulates growth hormone (GH) secretion in Wistar rats, and then investigated its mechanism. GH-releasing activity after intraduodenal administration of l-Orn was blocked by [d-Lys3]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn (100 µM) has no affinity for the ghrelin receptor, suggesting that the GH-releasing activity of l-Orn is mediated via ghrelin release and activation of the ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA expression in the duodenum but not in the stomach or hypothalamus. In addition, l-Orn-induced GH-releasing activity was inhibited by propranolol, an antagonist of ß-adrenergic receptor, which is known to be coupled to ghrelin release. In conclusion, intraduodenally administered l-Orn stimulates GH secretion through the sympathetic nervous and ghrelin systems.
Assuntos
Grelina/metabolismo , Hormônio do Crescimento/metabolismo , Ornitina/metabolismo , Animais , Duodeno/metabolismo , Hipotálamo/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores de Grelina/metabolismoRESUMO
It is well known that large dose of leucine reduces the food intake and causes growth retardation in experimental animals when leucine is given with a low-protein diet. However, the mechanism for the anorectic effect of leucine has not yet been clarified. We demonstrate here that the anorectic effect of leucine was significantly reduced in a vagotomized rat.