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L-Lysine Acts Like a Partial Serotonin Receptor 4 Antagonist and Inhibits Serotonin-Mediated Intestinal Pathologies and Anxiety in Rats

Miro Smriga and Kunio Torii
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 26 (Dec. 23, 2003), pp. 15370-15375
Stable URL: http://www.jstor.org/stable/3149012
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
L-Lysine Acts Like a Partial Serotonin Receptor 4 Antagonist and Inhibits Serotonin-Mediated Intestinal Pathologies and Anxiety in Rats
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Abstract

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.

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