期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：26
页码：15370-15375
DOI：10.1073/pnas.2436556100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The purpose of this investigation was to determine whether a nutritionally essential amino acid, L-lysine, acts like a serotonin receptor 4 (5-HT4) antagonist, and if L-lysine is beneficial in animal models of serotonin (5-HT)-induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress-induced fecal excretion. The radioligand-binding assay was used to test the binding of L-lysine to various 5-HT receptors. The effects of L-lysine on 5-HT-induced contractions of isolated guinea pig ileum were studied in vitro. The effects of oral administration of L-lysine on diarrhea, stress-induced fecal excretion, and 5-HT-induced corticosterone release, tachycardia, and anxiety (an elevated plus maze paradigm) were studied in rats in vivo. L-Lysine (0.8 mmol/dl) inhibited (9.17%) binding of 5-HT to the 5-HT4 receptor, without any effect on 5-HT1A,2A,2B,2C,3 binding. L-Lysine (0.07 and 0.7 mmol/dl) blocked 5-HT-induced contractions of an isolated guinea pig ileum in vitro (P < 0.05 and P < 0.01). Orally applied L-lysine (1 g/kg of body weight) inhibited (P < 0.12) diarrhea triggered by coadministration of restraint stress and 5-hydroxytryptophane (10 mg/kg of body weight), and significantly blocked anxiety induced by the 5-HT4 receptor agonist (3.0 mmol/liter) in rats in vivo. No effects of L-lysine or the 5-HT4 receptor agonist on plasma corticosterone and heart rate were recorded. L-Lysine may be a partial 5-HT4 receptor antagonist and suppresses 5-HT4 receptor-mediated intestinal pathologies and anxiety in rats. An increase in nutritional load of L-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions.
