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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Dec 17

PMID 14676321

Citations 27

Authors

Miro Smriga

Kunio Torii

Affiliations

Soon will be listed here.

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.

Citing Articles

Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression.

Naufel M, Pedroso A, de Souza A, Boldarine V, Oyama L, Lo Turco E Metabolites. 2024; 14(5).

PMID: 38786763 PMC: 11123176. DOI: 10.3390/metabo14050286.

Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants.

Alemany S, Soler-Artigas M, Cabana-Dominguez J, Fakhreddine D, Llonga N, Vilar-Ribo L J Transl Med. 2023; 21(1):272.

PMID: 37085903 PMC: 10120121. DOI: 10.1186/s12967-023-04107-5.

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa.

Liu X, Fang Y, Xu J, Yang T, Xu J, He J PLoS One. 2023; 18(3):e0282700.

PMID: 36917582 PMC: 10013885. DOI: 10.1371/journal.pone.0282700.

Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease.

Neumann J, Hofmann B, Dhein S, Gergs U Int J Mol Sci. 2023; 24(5).

PMID: 36902195 PMC: 10003731. DOI: 10.3390/ijms24054765.

Low-quality protein modulates inflammatory markers and the response to lipopolysaccharide insult: the case of lysine.

El-Mallah C, Ragi M, Eid A, Obeid O Br J Nutr. 2023; 130(6):944-957.

PMID: 36597807 PMC: 10442798. DOI: 10.1017/S0007114522004068.

References

Kilbinger H, Wolf D . Effects of 5-HT4 receptor stimulation on basal and electrically evoked release of acetylcholine from guinea-pig myenteric plexus. Naunyn Schmiedebergs Arch Pharmacol. 1992; 345(3):270-5. DOI: 10.1007/BF00168686. View

Hegde S, Eglen R . Peripheral 5-HT4 receptors. FASEB J. 1996; 10(12):1398-407. DOI: 10.1096/fasebj.10.12.8903510. View

Saitoh M, Muramatsu M . Identification and characterization of the 5-HT4 receptor in the intestinal tract and striatum of the guinea pig. Life Sci. 1996; 59(25-26):2129-37. DOI: 10.1016/s0024-3205(96)00569-3. View

Barclay G, Turnberg L . Effect of psychological stress on salt and water transport in the human jejunum. Gastroenterology. 1987; 93(1):91-7. DOI: 10.1016/0016-5085(87)90319-2. View

Centurion D, Ortiz M, Saxena P, Villalon C . The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype. Br J Pharmacol. 2002; 135(6):1531-9. PMC: 1573258. DOI: 10.1038/sj.bjp.0704593. View

Kennett G, Bright F, Trail B, Blackburn T, Sanger G . Anxiolytic-like actions of the selective 5-HT4 receptor antagonists SB 204070A and SB 207266A in rats. Neuropharmacology. 1997; 36(4-5):707-12. DOI: 10.1016/s0028-3908(97)00037-3. View

Sanger G, Yoshida M, Yahyah M, Kitazumi K . Increased defecation during stress or after 5-hydroxytryptophan: selective inhibition by the 5-HT(4) receptor antagonist, SB-207266. Br J Pharmacol. 2000; 130(3):706-12. PMC: 1572116. DOI: 10.1038/sj.bjp.0703367. View

Monnikes H, Tebbe J, Hildebrandt M, Arck P, Osmanoglou E, Rose M . Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity. Dig Dis. 2001; 19(3):201-11. DOI: 10.1159/000050681. View

Feigenbaum P, Chang Y . Pipecolic acid antagonizes barbiturate-enhanced GABA binding to bovine brain membranes. Brain Res. 1986; 372(1):176-9. DOI: 10.1016/0006-8993(86)91474-5. View

10.

Ressler K, Nemeroff C . Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000; 12 Suppl 1:2-19. DOI: 10.1002/1520-6394(2000)12:1+<2::AID-DA2>3.0.CO;2-4. View

11.

Banner S, Smith M, Bywater D, Gaster L, Sanger G . Increased defaecation caused by 5-HT4 receptor activation in the mouse. Eur J Pharmacol. 1996; 308(2):181-6. DOI: 10.1016/0014-2999(96)00296-8. View

12.

Tam F, Hillier K, Bunce K . Characterization of the 5-hydroxytryptamine receptor type involved in inhibition of spontaneous activity of human isolated colonic circular muscle. Br J Pharmacol. 1994; 113(1):143-50. PMC: 1510073. DOI: 10.1111/j.1476-5381.1994.tb16186.x. View

13.

Blanchard E, Scharff L, Schwarz S, Suls J, Barlow D . The role of anxiety and depression in the irritable bowel syndrome. Behav Res Ther. 1990; 28(5):401-5. DOI: 10.1016/0005-7967(90)90159-g. View

14.

Williams C, Villar R, Peterson J, Burks T . Stress-induced changes in intestinal transit in the rat: a model for irritable bowel syndrome. Gastroenterology. 1988; 94(3):611-21. DOI: 10.1016/0016-5085(88)90231-4. View

15.

Schoemaker R, Du X, Bax W, Bos E, Saxena P . 5-Hydroxytryptamine stimulates human isolated atrium but not ventricle. Eur J Pharmacol. 1993; 230(1):103-5. DOI: 10.1016/0014-2999(93)90417-g. View

16.

FLODIN N . The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr. 1997; 16(1):7-21. DOI: 10.1080/07315724.1997.10718644. View

17.

Haug T, Mykletun A, Dahl A . Are anxiety and depression related to gastrointestinal symptoms in the general population?. Scand J Gastroenterol. 2002; 37(3):294-8. DOI: 10.1080/003655202317284192. View

18.

Pauwels P . Diverse signalling by 5-hydroxytryptamine (5-HT) receptors. Biochem Pharmacol. 2000; 60(12):1743-50. DOI: 10.1016/s0006-2952(00)00476-7. View

19.

Young V, PELLETT P . Wheat proteins in relation to protein requirements and availability of amino acids. Am J Clin Nutr. 1985; 41(5 Suppl):1077-90. DOI: 10.1093/ajcn/41.5.1077. View

20.

Enck P, Merlin V, Erckenbrecht J, Wienbeck M . Stress effects on gastrointestinal transit in the rat. Gut. 1989; 30(4):455-9. PMC: 1434046. DOI: 10.1136/gut.30.4.455. View