L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats.
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.
Smriga
Miro
M
Ajinomoto Co, Inc., Institute of Life Sciences, Kawasaki 210-8681, Japan. miroslav_smriga@ajinomoto.com
Torii
Kunio
K
D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D003967:Diarrhea / Q000503:physiopathology / Q000517:prevention & control; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008239:Lysine; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects / Q000502:physiology*; D012149:Restraint, Physical; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000517:prevention & control
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D008239:Lysine