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Mechanisms and Significance of the Increased Brain Uptake of Tryptophan

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Abstract

Changes in brain tryptophan concentrations may affect the synthesis of brain serotonin (5-hydroxytryptamine, 5-HT). Concentrations of tryptophan are regulated more than those of any other amino acid. Such stimuli as acute stress, carbohydrate ingestion, and treatment with various drugs increase the brain content of tryptophan. Treatment of rats and mice with interleukin-1 (IL-1), interleukin-6 (IL-6), lipopolysaccharide (LPS), and β-adrenoceptor agonists, as well as a variety of stressors, such as footshock and restraint, all increase brain concentrations of tryptophan. The peak effect following both acute stress and β-adrenoceptor agonist administration occurs within 30–60 min, whereas the peak effect following LPS and the cytokines occurs much later at around 4–8 h. Experiments using the ganglionic blocker chlorisondamine, and β-adrenoceptor antagonists suggest that the sympathetic nervous system plays an important role in the modulation of brain tryptophan concentrations. The mechanisms involved in the increases observed in brain tryptophan are discussed, as well as their possible biological significance.

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References

  1. D. Eccleston G. W. Ashcroft T. B. Crawford (1965) ArticleTitle5-hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading. II. Applications and drug studies J. Neurochem. 12 493–503 Occurrence Handle5294373 Occurrence Handle1:STN:280:CCmD3M7ntFU%3D Occurrence Handle10.1111/j.1471-4159.1965.tb06776.x

    Article  PubMed  CAS  Google Scholar 

  2. A. T. Moir D. Eccleston (1968) ArticleTitleThe effects of precursor loading in the cerebral metabolism of 5- hydroxyindoles J.␣Neurochem. 15 1093–1108 Occurrence Handle5304606 Occurrence Handle1:CAS:528:DyaF1cXkvFChtLc%3D Occurrence Handle10.1111/j.1471-4159.1968.tb06827.x

    Article  PubMed  CAS  Google Scholar 

  3. G. Curzon M. H. Joseph P. J. Knott (1972) ArticleTitleEffects of immobilization and food deprivation on rat brain tryptophan metabolism J. Neurochem. 19 1967–1974 Occurrence Handle5047857 Occurrence Handle1:CAS:528:DyaE38XltFWru7o%3D Occurrence Handle10.1111/j.1471-4159.1972.tb01486.x

    Article  PubMed  CAS  Google Scholar 

  4. J. D. Fernstrom (1979) ArticleTitleDiet-induced changes in plasma amino acid pattern: effects on the brain uptake of large neutral amino acids, and on brain serotonin synthesis J. Neural Transm. 15 IssueIDsuppl 55–67 Occurrence Handle1:CAS:528:DyaL3MXksVWjtbY%3D

    CAS  Google Scholar 

  5. W. M. Pardridge (1977) ArticleTitleKinetics of competitive inhibition of neutral amino acid transport across the blood-brain barrier J. Neurochem. 28 103–108 Occurrence Handle833586 Occurrence Handle1:CAS:528:DyaE2sXktVaqtbs%3D Occurrence Handle10.1111/j.1471-4159.1977.tb07714.x

    Article  PubMed  CAS  Google Scholar 

  6. W. M. Pardridge (1998) Targeted delivery of hormones to tissues by plasma proteins. Handbook of Physiology – Cellular Mechanisms P. M. Conn (Eds) Handbook of Physiology – Cellular Mechanisms Oxford University Press New York

    Google Scholar 

  7. A. J. Dunn (1992) ArticleTitleEndotoxin-induced activation of cerebral catecholamine and serotonin metabolism - comparison with interleukin-1 J. Pharmacol. Exp. Ther. 261 964–969 Occurrence Handle1602402 Occurrence Handle1:CAS:528:DyaK38XksVKgt7Y%3D

    PubMed  CAS  Google Scholar 

  8. A. J. Dunn (1993) ArticleTitleNitric oxide synthase inhibitors prevent the cerebral tryptophan and serotonergic responses to endotoxin and interleukin-1 Neurosci. Res. Comm. 13 149–156 Occurrence Handle1:CAS:528:DyaK2cXivV2rtbc%3D

    CAS  Google Scholar 

  9. A. J. Dunn J Welch (1991) ArticleTitleStress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity J. Neurochem. 57 1615–1622 Occurrence Handle1717650 Occurrence Handle1:CAS:528:DyaK3MXmsFaqt7g%3D Occurrence Handle10.1111/j.1471-4159.1991.tb06359.x

    Article  PubMed  CAS  Google Scholar 

  10. M. P. Heyes B. J. Quearry S. P. Markey (1989) ArticleTitleSystemic endotoxin increases L-tryptophan, 5-hydroxyindoleacetic acid, 3-hydroxykynurenine and quinolinic acid content of mouse cerebral cortex Brain Res. 491 173–179 Occurrence Handle2475209 Occurrence Handle10.1016/0006-8993(89)90101-7 Occurrence Handle1:CAS:528:DyaL1MXltFSks7Y%3D

    Article  PubMed  CAS  Google Scholar 

  11. A. J. Dunn (1988) ArticleTitleSystemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone Life Sci. 43 429–435 Occurrence Handle3260987 Occurrence Handle1:CAS:528:DyaL1cXksFaqtbg%3D Occurrence Handle10.1016/0024-3205(88)90522-X

    Article  PubMed  CAS  Google Scholar 

  12. A. Kabiersch A. Rey Particledel C. G. Honegger H. O. Besedovsky (1988) ArticleTitleInterleukin-1 induces changes in norepinephrine metabolism in the rat brain Brain Behav. Immun. 2 267–274 Occurrence Handle3266560 Occurrence Handle10.1016/0889-1591(88)90028-1 Occurrence Handle1:CAS:528:DyaL1MXhvFSrtb0%3D

    Article  PubMed  CAS  Google Scholar 

  13. A. J. Dunn (2000) ArticleTitleEffects of the IL-1 receptor antagonist on the IL-1- and endotoxin- induced activation of the HPA axis and cerebral biogenic amines in mice Neuroimmunomodulation 7 36–45 Occurrence Handle10601817 Occurrence Handle10.1159/000026418 Occurrence Handle1:CAS:528:DC%2BD3cXjsVSisA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  14. C. Libert P. Brouckaert A. Shaw W. Fiers (1990) ArticleTitleInduction of interleukin-6 by human and recombinant interleukin-1 in mice Eur. J. Immunol. 20 691–694 Occurrence Handle2318254 Occurrence Handle1:CAS:528:DyaK3cXitlektro%3D Occurrence Handle10.1002/eji.1830200333

    Article  PubMed  CAS  Google Scholar 

  15. M. Shalaby A. Waage L. Aarden T. Espevik (1989) ArticleTitleEndotoxin, tumor necrosis factor-alpha and interleukin-1 induce interleukin-6 production in vivo Clin. Immunol. Immunopathol. 53 488–498 Occurrence Handle2805453 Occurrence Handle10.1016/0090-1229(89)90010-X Occurrence Handle1:CAS:528:DyaK3cXnsFSjsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  16. T. H. Jones (1994) ArticleTitleInterleukin-6 as an endocrine cytokine Clin. Endocrinol. 40 703–713 Occurrence Handle1:CAS:528:DyaK2cXltlWktb8%3D Occurrence Handle10.1111/j.1365-2265.1994.tb02502.x

    Article  CAS  Google Scholar 

  17. J. P. Wang A. J. Dunn (1998) ArticleTitleMouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism Neurochem. Int. 33 143–154 Occurrence Handle9761458 Occurrence Handle10.1016/S0197-0186(98)00016-3 Occurrence Handle1:CAS:528:DyaK1cXmt1Kgt70%3D

    Article  PubMed  CAS  Google Scholar 

  18. F. Chaouloff D. Laude E. Mignot P. Kamoun J. L. Elghozi (1985) ArticleTitleTryptohan and serotonin turnover rate in the brain of genetically hyperammonemic mice Neurochem. Int. 7 143–153 Occurrence Handle10.1016/0197-0186(85)90019-1 Occurrence Handle1:CAS:528:DyaL2MXktlalsLs%3D

    Article  CAS  Google Scholar 

  19. A. J. Dunn (1988) ArticleTitleChanges in plasma and brain tryptophan and brain serotonin and 5- hydroxyindoleacetic acid after footshock stress Life Sci. 42 1847–1853 Occurrence Handle2452945 Occurrence Handle10.1016/0024-3205(88)90023-9 Occurrence Handle1:CAS:528:DyaL1cXhvFyrsLk%3D

    Article  PubMed  CAS  Google Scholar 

  20. A. J. Dunn (1988) ArticleTitleStress-related changes in cerebral catecholamine and indoleamine metabolism: lack of effect of adrenalectomy and corticosterone J. Neurochem. 51 406–412 Occurrence Handle2455773 Occurrence Handle1:CAS:528:DyaL1cXkvVKrtrw%3D Occurrence Handle10.1111/j.1471-4159.1988.tb01053.x

    Article  PubMed  CAS  Google Scholar 

  21. D. J. Edwards D. A. Sorisio S. Knopf (1989) ArticleTitleEffects of the beta 2-adrenoceptor agonist clenbuterol on tyrosine and tryptophan in plasma and brain of the rat Biochem. Pharmacol. 38 2957–2965 Occurrence Handle2551300 Occurrence Handle10.1016/0006-2952(89)90003-8 Occurrence Handle1:CAS:528:DyaL1MXlvVOgu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  22. N. R. Lenard T. W. Gettys A. J. Dunn (2003) ArticleTitleActivation of beta2- and beta3-adrenergic receptors increases brain tryptophan J. Pharmacol. Exp. Ther. 305 653–659 Occurrence Handle12606631 Occurrence Handle10.1124/jpet.102.048249 Occurrence Handle1:CAS:528:DC%2BD3sXjt12mu78%3D

    Article  PubMed  CAS  Google Scholar 

  23. Y. Takao Y. Kamisaki T. Itoh (1992) ArticleTitleBeta-adrenergic regulation of amine precursor amino acid transport across the blood-brain barrier Eur. J. Pharmacol. 215 245–251 Occurrence Handle1356793 Occurrence Handle10.1016/0014-2999(92)90034-2 Occurrence Handle1:CAS:528:DyaK38XksVWisLw%3D

    Article  PubMed  CAS  Google Scholar 

  24. N. R. Lenard A. J. Dunn (2004) ArticleTitleIncreased insulin is not required for beta-2-adrenoceptor-induced increases in mouse brain tryptophan Eur. J. Pharmacol. 497 105–110 Occurrence Handle15321741 Occurrence Handle10.1016/j.ejphar.2004.06.031 Occurrence Handle1:CAS:528:DC%2BD2cXmsVGnsr4%3D

    Article  PubMed  CAS  Google Scholar 

  25. N. R. Lenard A. J. Dunn (2005) ArticleTitlePotential role for nonesterified fatty acids in beta-adrenoceptor-induced increases in brain tryptophan Neurochem. Int. 46 179–187 Occurrence Handle15627518 Occurrence Handle10.1016/j.neuint.2004.07.010 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGhtbnM

    Article  PubMed  CAS  Google Scholar 

  26. J. Wang A. J. Dunn (1999) ArticleTitleThe role of interleukin-6 in the activation of the hypothalamo-pituitary-adrenocortical axis and brain indoleamines by endotoxin and interleukin-1 beta Brain Res. 815 337–348 Occurrence Handle9878816 Occurrence Handle10.1016/S0006-8993(98)01091-9 Occurrence Handle1:CAS:528:DyaK1MXhsVWqug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  27. S. B. Jones F. D. Romano (1984) ArticleTitlePlasma catecholamines in the conscious rat during endotoxicosis Circulatory Shock 14 189–201 Occurrence Handle6391720 Occurrence Handle1:CAS:528:DyaL2MXit1amsw%3D%3D

    PubMed  CAS  Google Scholar 

  28. J. R. Weinberg D. J. Wright A. Guz (1988) ArticleTitleInterleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit Clin. Sci. (London) 75 251–255 Occurrence Handle1:CAS:528:DyaL1cXlt1OisLk%3D

    CAS  Google Scholar 

  29. G. Strassmann M. Fong J. S. Kenney C. O. Jacob (1992) ArticleTitleEvidence for the involvement of interleukin-6 in experimental cancer cachexia J. Clin. Invest. 89 1681–1684 Occurrence Handle1569207 Occurrence Handle1:CAS:528:DyaK38XisFehs7Y%3D Occurrence Handle10.1172/JCI115767

    Article  PubMed  CAS  Google Scholar 

  30. B. E. Levin A. C. Sullivan (1987) ArticleTitleGlucose, insulin, and sympathoadrenal activation J. Autonomic Nerv. Sys. 20 233–242 Occurrence Handle1:CAS:528:DyaL1cXmvFCmtA%3D%3D Occurrence Handle10.1016/0165-1838(87)90152-4

    Article  CAS  Google Scholar 

  31. A. Scheurink S. Ritter (1993) ArticleTitleSympathoadrenal responses to glucoprivation and lipoprivation in rats Physiol. Behav. 53 995–1000 Occurrence Handle8511217 Occurrence Handle1:CAS:528:DyaK3sXksVyhu7g%3D Occurrence Handle10.1016/0031-9384(93)90279-O

    Article  PubMed  CAS  Google Scholar 

  32. E. Nisoli M. O. Carruba (1997) ArticleTitlePharmacological properties of beta 3-adrenoceptors Trends Pharmacol. Sci. 18 257–258 Occurrence Handle9253858 Occurrence Handle10.1016/S0165-6147(97)90634-9 Occurrence Handle1:CAS:528:DyaK2sXkvVaqurY%3D

    Article  PubMed  CAS  Google Scholar 

  33. M. Ito D. Grujic E. D. Abel A. Vidal-Puig V. S. Susulic J. Lawitts M. E. Harper J. Himms-Hagen A. D. Strosberg B. B. Lowell (1998) ArticleTitleMice expressing human but not murine beta3-adrenergic receptors under the control of human gene regulatory elements Diabetes 47 1464–1471 Occurrence Handle9726236 Occurrence Handle1:CAS:528:DyaK1cXlslSjt74%3D Occurrence Handle10.2337/diabetes.47.9.1464

    Article  PubMed  CAS  Google Scholar 

  34. M. Bamshad C. K. Song T. J. Bartness (1999) ArticleTitleCNS origins of the sympathetic nervous system outflow to brown adipose tissue Am. J. Physiol. 276 R1569–1578 Occurrence Handle10362733 Occurrence Handle1:CAS:528:DyaK1MXksVWmsLw%3D

    PubMed  CAS  Google Scholar 

  35. H. N. Christensen (1990) ArticleTitleRole of amino acid transport and countertransport in nutrition and metabolism Physiol. Rev. 70 43–77 Occurrence Handle2404290 Occurrence Handle1:CAS:528:DyaK3cXpsF2hsQ%3D%3D

    PubMed  CAS  Google Scholar 

  36. Y. Kanai H. Segawa K. Miyamoto H. Uchino E. Takeda H. Endou (1998) ArticleTitleExpression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98) J. Biol. Chem. 273 23629–23632 Occurrence Handle9726963 Occurrence Handle10.1074/jbc.273.37.23629 Occurrence Handle1:CAS:528:DyaK1cXmtFOktLo%3D

    Article  PubMed  CAS  Google Scholar 

  37. L. Mastroberardino B. Spindler R. Pfeiffer P. J. Skelly J. Loffing C. B. Shoemaker F. Verrey (1998) ArticleTitleAmino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family Nature 395 288–291 Occurrence Handle9751058 Occurrence Handle1:CAS:528:DyaK1cXmtFejsb4%3D Occurrence Handle10.1038/26246

    Article  PubMed  CAS  Google Scholar 

  38. O. Durieu-Trautmann N. Foignant A. D. Strosberg P. O. Couraud (1991) ArticleTitleCoexpression of beta 1- and beta 2-adrenergic receptors on bovine brain capillary endothelial cells in culture J. Neurochem. 56 775–781 Occurrence Handle1847183 Occurrence Handle1:CAS:528:DyaK3MXhtFGltL8%3D Occurrence Handle10.1111/j.1471-4159.1991.tb01991.x

    Article  PubMed  CAS  Google Scholar 

  39. H. Matsuo S. Tsukada T. Nakata A. Chairoungdua D. K. Kim S. H. Cha J. Inatomi H. Yorifuji J. Fukuda H. Endou Y. Kanai (2000) ArticleTitleExpression of a system L neutral amino acid transporter at the blood-brain barrier Neuroreport 11 3507–3511 Occurrence Handle11095508 Occurrence Handle1:CAS:528:DC%2BD3cXosFKntb8%3D Occurrence Handle10.1097/00001756-200011090-00021

    Article  PubMed  CAS  Google Scholar 

  40. R. L. O’Kane R. A. Hawkins (2003) ArticleTitleNa+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier Am. J. Physiol. Endocrinol. Metab. 285 E1167–1173 Occurrence Handle12933350 Occurrence Handle1:CAS:528:DC%2BD2cXhtlWk

    PubMed  CAS  Google Scholar 

  41. M. H. Joseph G. A. Kennett (1983) ArticleTitleStress-induced release of 5-HT in the hippocampus and its dependence on increased tryptophan availability: an in vivo electrochemical study Brain Res. 270 251–257 Occurrence Handle6224532 Occurrence Handle10.1016/0006-8993(83)90598-X Occurrence Handle1:CAS:528:DyaL3sXkvVaqu7o%3D

    Article  PubMed  CAS  Google Scholar 

  42. M. H. Joseph G. A. Kennett (1983) ArticleTitleCorticosteroid response to stress depends upon increased tryptophan availability Psychopharmacology 79 79–81 Occurrence Handle6403969 Occurrence Handle10.1007/BF00433020 Occurrence Handle1:CAS:528:DyaL3sXms1Shtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

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  1. Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Natalie R. Lenard

  2. Department of Pharmacology, Toxicology, and Neuroscience, LSU Health Sciences Center-Shreveport, 1501 Kings Highway Shreveport, 71103, LA, USA

    Adrian J. Dunn

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Special issue dedicated to Dr. Simo S. Oja

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Lenard, N.R., Dunn, A.J. Mechanisms and Significance of the Increased Brain Uptake of Tryptophan. Neurochem Res 30, 1543–1548 (2005). https://doi.org/10.1007/s11064-005-8832-x

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