Taurine 4 pp 35-44 | Cite as

Mode of Action of Taurine and Regulation Dynamics of Its Synthesis in the CNS

  • Jang-Yen Wu
  • Weiqing Chen
  • Xiao Wen Tang
  • Hong Jin
  • Todd Foos
  • John V. Schloss
  • Kathleen Davis
  • Morris D. Faiman
  • Che-Chang Hsu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 483)


The regulation of taurine biosynthesis can be summarized as following: (i) When neurons are stimulated, the arrival of action potential will open the voltage-dependent Ca2+-channel, resulting in an increase of intracellular free Ca2+, [Ca2+]i, (ii) Elevation of [Ca2+]i will trigger release of taurine as well as activation of PKC, which in turn activates CSAD through protein phosphorylation; (iii) The activated CSAD then synthesizes more taurine to replenish that lost due to stimulation-mediated release; (iv) When intracellular taurine reach a certain level, it then inhibits the activation of PKC directly or indirectly (possibly through regulating Ca2+ availability), thus shutting down activation of CSAD through inhibition of CSAD phosphorylation by PKC; and (v) CSAD soon returns to its inactive state through the action of a protein phosphatase, most likely PrP-2C. The mode of action of taurine inlowering the level of [Ca2+]i, is at least partially due to its inhibition on the reverse mode of Na+-Ca2+ exchanger activity


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Almarghini, K., Barbagli, B., and Tappaz, M., 1994, Production and characterization of a new specific antiserum against the taurine putative biosynthetic enzyme cysteine sulfinate decarboxylase. J. Neurochem. 62:1604–1614.Google Scholar
  2. 2.
    Almarghini, K., Remy, A., and Tappaz, M., 1991, Immunocyto-chemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase in the cerebellum. Evidence for a glial localization. Neuroscience 43:111–119.Google Scholar
  3. 3.
    Bao, J., Cheung, W. Y., and Wu, J.-Y., 1995, Brain L-glutamate decarboxylase: Inhibition by phosphorylation and activation by dephosphorylation. J. Biol. Chem. 270:6464–6467.Google Scholar
  4. 4.
    Bao, J., Nathan, B., and Wu, J.-Y., 1994, Role of protein phos-phorylation in the regulation of brain L-glutamate decarboxylase activity. J. Biomed. Sci. 1:237–244.Google Scholar
  5. 5.
    Blaustein, M.P., 1989, Calcium transport and buffering in neurons. Trends Neurosci. 11: 438–443.Google Scholar
  6. 6.
    Blinderman, J. M., Maitre, M., Ossola, L., and Mandel, P., 1978, Purification and some properties of L-glutamate decarboxylase from human brain. Eur. J. Biochem. 86:143–152.Google Scholar
  7. 7.
    Chan-Palay, V., Lin, C. T., Palay, S., Yamamoto, M., and Wu, J.-Y., 1982, Taurine in the mammalian cerebellum: Demonstration by autoradiography with [3H]taurine and immunocytochemistry with antibodies against the taurine-synthesizing enzyme, cysteine sulfinic acid decarboxylase. Proc. Natl. Acad. Sci. USA 79:2695–2699.Google Scholar
  8. 8.
    Chan-Palay, V., Palay, S., Li, C., and Wu, J.-Y., 1982, Sagittal cerebellar micro-bands of taurine neurons: Immunocytochemical demonstration by using antibodies against the taurine synthesizing enzyme cysteine sulfinic acid decarboxylase. Proc. Natl. Acad. Sci. USA 79:4221–4225.Google Scholar
  9. 9.
    Chazov, E.I., Malchikova, L.S., Lipina, N.V., Asafov, G.B., and Smirnov, V.N., 1974, Taurine and electrical activity of the heart. Circ. Res. 34/35SIII:III-11-III-21.Google Scholar
  10. 10.
    Chen, X.-C., Pan, Z.-L., Liu, D.-S., and Han, X.B., 1998, Effect of taurine on human fetal neuron cells: Proliferation and differentiation. In Adv. Exp. Med. Biol., “Taurine 3: Cellular and Regulatory Mechanisms”, Schaffer, S., Lombardini, J.B. and Huxtable, R.J., eds., Plenum Press, New York, 442:397–403.Google Scholar
  11. 11.
    Davison, A.V., 1956, Amino acid decarboxylase in rat brain and liver. Biochem. Biophys. Acta. 234:107–108.Google Scholar
  12. 12.
    Green, P., Dawson, R., Wallace, D.R., and Owens, J., 1998, Treatment of rat brain membranes with taurine increases radioligand binding. In Adv. Exp. Med. Biol., “Taurine3: Cellular and Regulatory Mechanisms”, Schaffer, S., Lombardini, J.B. and Huxtable, R.J., eds., Plenum Press, New York, 442:377–383.Google Scholar
  13. 13.
    Han, X., Budreau, A.M., and Chesney, R.W., 1998, Molecular cloning and functional expression of LLC-PK1 cell taurine transporter that is adaptively regulated by taurine. Adv. In Expt. Med. & Biol. 442:261–268.Google Scholar
  14. 14.
    Hasal, S.J., Sun, Y., Yan, C.C., Brendel, K., and Huxtable, R.J., 1998, Effects of taurine in percision-cut liver slices exposed to the pyrrolizidine alkaloid, retrorsine. In Adv. Exp. Med. Biol., “Taurine3: Cellular and Regulatory Mechanisms”, Schaffer, S., Lombardini, J.B. and Huxtable, R.J., eds., Plenum Press, New York, 442:79–83.Google Scholar
  15. 15.
    Hayes, K., Rabin, A., and Berson, E., 1975, An ultrastructural study of nutritionally induced and reversed retinal degeneration in cats. Am. J. Pathol. 78:505.Google Scholar
  16. 16.
    Hayes, K., Carey, R.E., and Schmidt, S.Y., 1975, Retinal degeneration associated with taurine deficiency in the cat. Science 188:949–951.Google Scholar
  17. 17.
    Huxtable, R.J., 1989, Taurine in the central nervous system and the mammalian actions of taurine. Prog. Neurobiol. 32:471–533.Google Scholar
  18. 18.
    Huxtable, R.J., 1992, Physiological actions of taurine. Physiol. Rev. 72: 101–163.Google Scholar
  19. 19.
    Huxtable, R.J., and Bressler, R., 1973, Effect of taurine on a muscle intracellular membrane. Biochem. Biophys. Acta. 323:573–583.Google Scholar
  20. 20.
    Izumi, K., Donaldson, J., Minnich, J.L., and Barbeau, A,. 1973, Ouabain-induced seizures in rats: suppression effects of taurine and g-aminobutyric acid. Can. J. Physiol. Pharmacol. 51:885–889.Google Scholar
  21. 21.
    Izumi, K., Igisu, H., and Fukuda, T., 1974, Suppression of seisures by taurine specific or non-specific? Brain Res. 76:171–173.Google Scholar
  22. 22.
    Jacobsen, J.G., and Smith, L.H., 1968, Biochemistry and physiology of taurine and taurine derivatives. Physiol. Rev. 48:424–511.Google Scholar
  23. 23.
    Jerkins, A.A.; Bobroff, L.E., and Steele, R.D., 1989, Hepatic cysteine sulfinic acid decarboxylase activity in rat fed various levels of dietary casein. J. Nutri. 119: 1593–1597.Google Scholar
  24. 24.
    Jerkins, A.A., and Steele, R.D., 1991, Dietary sulfur amino acid modulation of cysteine sulfinic acid decarboxylase. Am. J. Physiol. 261:551–555.Google Scholar
  25. 25.
    Jerkins, A.A., and Steele, R.D., 1991, Cysteine sulfinic acid decarboxylase activity in response to thyroid homone administration in rats. Arch. Biochem. Biophys. 286:428–432.Google Scholar
  26. 26.
    Jerkins, A.A., and Steele, R.D., 1992, Quantification of cysteine sulfinic acid decarboxylase in male and female rats: Effect of adrenalectomy and methionine. Arch. Biochim. Biophys. 294:534–538.Google Scholar
  27. 27.
    Kaisakia, P.J., Jerkins, A.A., Goodspeed, D.C., and Steele, R.D., 1995, Cloning and characterization of rat cysteine sulfinic acid decarboxylase. Biochim. Biophys. Acta. 1262:79–82.Google Scholar
  28. 28.
    Kramer, J.H., Chivan, J.P., and Schaffer, S.W., 1981, Effect oftaurine on calcium paradox and ischemic heart failure. Am. J. Physiol. 240:H238–246.Google Scholar
  29. 29.
    Kuriyama, K., 1980, Taurine as a neuromodulator. Fed. Proc. 39:2680–2684.Google Scholar
  30. 30.
    Lazarewicz, J.W., Noremberg, K., Lehmann, A., and Hamberger, A., 1985, Effects of taurine on calcium binding and accumulation in rabbit hippocampal and cortical synaptosomes. Neurochem. Int. 7:421–428.Google Scholar
  31. 31.
    Lee, Y.-H., Deupree, D.L., Chen, S.-C., Kao, L.-S., and Wu, J.-Y,. 1994, Role of Ca2+ in a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated polyphosphoinositide turnover in primary neuronal cultures. J. Neurochem. 62:2325–2332.Google Scholar
  32. 32.
    Li, Y.P., and Lombardini, J.B., 1991, Taurine inhibits protein kinase C catalyzed phosphorylation of specific proteins in a rat cortical P2 fraction. J. Neurochem. 56:1747–1753.Google Scholar
  33. 33.
    Lin, C.-T., Li, H.-Z., and Wu, J.-Y., 1983, Immunocytochemical localization of L-glutamate decarboxylase, gamma aminobutyric acid transaminase, cysteine-sulfinic acid decarboxylase, aspartate aminotransferase and somatostatin in rat retina. Brain Res. 270: 273–283.Google Scholar
  34. 34.
    Lin, C.-T., Su, Y.Y.T., Song, G.-X., and Wu, J.-Y., 1985, Is taurine a neurotransmitter in rabbit retina? Brain Res. 337:293–298.Google Scholar
  35. 35.
    Lin, C.-T., Song, G.-X., and Wu, J.-Y., 1985, Ultrastructural demonstration of L-glutamate decarboxylase and cysteine sulfinic acid decarboxylase in rat retina by immunocytochemistry. Brain Res. 331:71–80.Google Scholar
  36. 36.
    Liu, Q.R., Lopez-Corcuera, B., Nelson, H., Mandiyan, S., and Nelson, N., 1992, Cloning and expression of a cDNA encoding the transporter of taurine and beta-alanine in mouse brain. Proc. Natl. Acad. Sci. USA 89:12145–12149.Google Scholar
  37. 37.
    Lombardini, J.B., Schaffer, S.W., and Azuma, J., (eds.), 1992, Taurine: Nutritional value and mechanisms of action. Adv. Expt. Med. & Biol. 315:1–441.Google Scholar
  38. 38.
    Magnusson, K.R., Madl, J.E., Clements, J.R., Wu, J.-Y., Larson, A.A., and Beitz, A.J., 1988, Co-localization of taurine-and cysteine sulfinic acid decarboxylase-like immunoreactivity in the cerebellum of the rat with the use of a novel monoclonal antibody against taurine. J. Neurosci. 8:4551–4564.Google Scholar
  39. 39.
    Magnusson, K.R., Clements, J.R., Wu, J.-Y., and Beitz, A.J., 1989, Co-localization of taurine-and cysteine sulfinic acid decarboxylase-like immunoreactivity in the hippocampus of the rat. Synapse 4:55–69.Google Scholar
  40. 40.
    Matsuda, T., Gemba, T., Baba, A., and Iwata, H., 1989, Inhibition by taurine of Na+-Ca2+ exchange in sarcolemmal membrane vesicles from bovine and guinea pig hearts. Comp. Biochem. Physiol. 94C(1):335–339.Google Scholar
  41. 41.
    Mutani, R., Bergamini, L., Fariello, R., and Delsedime, M., 1974, Effect of taurine on accut epileptic foci. Brain Res. 70:170–173.Google Scholar
  42. 42.
    Mutani, R., Monaco, F., Durelli, L., and Delsedime, M., 1975, Level of free amino acids in serum and cerebrospinal fluid after administration of taurine to epileptic and normal subjects. Epilepsia 16:765–769.Google Scholar
  43. 43.
    Oertel, W.H., Schmechel, D.E., Weise, V.K., Ransom, D.H., Tappaz, M.L., Krutzsch, H.C., and Kopin, I.J., 1981, Comparison of cysteine sulfinic acid decarboxylase isoenzymes and glutamic acid decarboxylase in rat liver and brain. Neuroscience 6:2701–2714.Google Scholar
  44. 44.
    Oja, S.S., and Kontro, P., 1983, Taurine. In Handbook of Neurochemistry Vol3, 2nd edn, edited by Lajtha, A, Plenum press, New York, p. 501–533.Google Scholar
  45. 45.
    Okamoto, K., Kimura, H., and Sakai, Y., 1983, Evidence for taurine as an inhibitory neurotransmitter in cerebellar stellate interneurons: Selective antagonism by TAG (6-aminomethyl-3-methyl-4H, 1, 2,4-benzothiadiazine-1, 1-dioxide). Brain Res. 265:163–168.Google Scholar
  46. 46.
    Reichert, P., and Urban, P.F., 1986, Purification and properties of rat brain cysteine sulfinate decarboxylase (E. C. Neurochem. Int. 9:315–321.Google Scholar
  47. 47.
    Remy, A, Henry, S., and Tappaz, M., 1990, Specific antiserum and monoclonal antibodies against the taurine biosynthesis-enzyme cysteine sulfinate decarboxylase: Identity of brain and liver enzyme. J. Neurochem. 54:870–879.Google Scholar
  48. 48.
    Sturman, J.A., Wen, G.Y., Wisniewski, H.M., and Neuringer, M.D., 1984, Retinal degeneration in primates raised on a synthetic human infant formula. Int. J. Dev. Neurosci. 2: 121–130.Google Scholar
  49. 49.
    Sturman, J.A., 1993, Taurine in development. Physiol. Rev. 73:119–147.Google Scholar
  50. 50.
    Sturman, J.A., and Chesney, R., 1995, Taurine in pediatric nutrition. Pediatr. Clin. N. Amer. 42(4):879–897.Google Scholar
  51. 51.
    Sumizu, K., 1962, Oxidation of hypotaurine in rat liver. Biochim. Biophys. Acta. 63:210–212.Google Scholar
  52. 52.
    Taber, T.C., Lin, C.-T., Song, G.-X., Thalman, R.H., and Wu, J.-Y., 1986, Taurine in the rat hippocampus-localization and postsynaptic action. Brain Res. 386:113–121.Google Scholar
  53. 53.
    Takahashi, K., Harada, H., Schaffer, S.W., and Azuma, J., 1992, Effect of taurine on intracellular calcium dynamics of cultured myocardial cells during the calcium paradox. In Adv. Exp. Med. Biol., “Taurine: Nutritional Value and Mechanisms of Action”, Lombardini, J.B., Schaffer, S.W. and Azuma, J., eds., Plenum Press, New York, 315:153–161.Google Scholar
  54. 54.
    Takuma, K., Matsuda, T., Hashimoto, H., Asano, S.,and Baba, A., 1994, Cultured rat astrocytes possess Na+-Ca2+ exchanger. Glia 12:336–342.Google Scholar
  55. 55.
    Tang, X.-W., Deupree, D.L., Sun, Y., and Wu, J.-Y., 1996, Biphasic effect of taurine on excitatory amino acid-induced neurotoxicity. In Adv. Exp. Med. Biol., “Taurine2: Basic and Clinical Aspects”, Huxtable, R.J., Azuma, J., Kuriyama, K., Nakagawa, M., and Baba, A., eds., Plenum Press, New York, 403:499–505.Google Scholar
  56. 56.
    Tang, X.W., Hsu, C.C., Schloss, J.V., Faiman, M.D., Wu, E., Yang, C.-Y., and Wu, J.-Y., 1997, Protein phosphorylation and taurine biosynthesis in vivo and in vitro. J. Neuroscience 17:6947–6951.Google Scholar
  57. 57.
    Tappaz, M., Almarghini, K., Legay, F., and Remy, A., 1992, Taurine biosynthesis enzyme cysteine sulfinate decarboxylase (CSD) from brain: the long and tricky trail to identification. Neurochem. Res. 17:849–859.Google Scholar
  58. 58.
    Thursby, M.H., and Nevis, A.H., 1974, Anticonvulsant activity of taurine in electrically and osmotically induced seizures in mice and rats. Fed. Proc. 33:1494.Google Scholar
  59. 59.
    Trenkner, E., Gargano, A., Scala, P., and Sturman, J., 1992, Taurine synthesis in cat and mouse in vivo and in vitro. Adv. Expt. Med. Biol. 315:7–14.Google Scholar
  60. 60.
    Tsukada, Y., Inoue, N., Donaldson, J., and Barbeau, A., 1974, Suppressive effects of various amino acids against ouabain-induced seizures in rats. Can. J. Neurol. Sci. 1:214–221Google Scholar
  61. 61.
    Uchida, S., Kwon, H.M., Yamauchi, A., Preston, A.S., Marumo, F., and Handler, J.S., 1992, The molecular cloning of the cDNA for an MDCK cell Na(+)-and Cl(-)-dependent taurine transporter that is regulated by hypertonicity. Proc. Natl. Acad. Sci. USA 89: 8230–8234.Google Scholar
  62. 62.
    van Gelder, N.M., and Courtois, A., 1972, Close correlation between changing content of specific amino acids in epileptogenic cortex of cats, and severity of epilepsy. Brain Res. 43:477–484.Google Scholar
  63. 63.
    Wang, G.X., Duan, J., Zhou, S., Li, P., and Kang, Y., 1992, Antiarrhythmic action of taurine. In Adv. Exp. Med. Biol., “Taurine: Nutritional Value and Mechanisms of Action”, Lombardini, J.B., Schaffer, S.W. and Azuma, J., eds., Plenum Press, New York, 315:187–192.Google Scholar
  64. 64.
    Welty, J.D., and McBroom, M.J., 1985, Effects of taurine on subcellular calcium dynamics in the normal and cardiomyopathic hamster heart. In The Effect of Taurine on Excitable Tissues, S.W. Schaffer, S.I. Baskin and J.J. Kocsis, eds., Spectrum Publications, New York, pp. 295–312.Google Scholar
  65. 65.
    Wright, C.E., Tallan, H.H., and Lin, Y.Y., 1986, Taurine: Biological update. Ann. Rev. Biochem. 55:427–453.Google Scholar
  66. 66.
    Wu, J.-Y., Su, Y.Y.T., Brandon, C., Lam, D.M.K., Chen, M.S., and Huang, W.M., 1979, Purification and immunochemical studies of GABA-, acetylcholine-and taurine-synthesizing enzymes from bovine and fish brains. Seventh International Meeting of the ISN, p. 662.Google Scholar
  67. 67.
    Wu, J.-Y., 1982, Purification and characterization of cysteic/cysteinesulfinic acids decarboxylase and L-glutamate decarboxylase in bovine brain. Proc. Natl. Acad. Sci. USA 79: 4270–4274.Google Scholar
  68. 68.
    Yan, C.C., and Huxtable, R.J., 1998, Effect of taurine on biliary metabolites of glutathione in liver perfused with the pyrrolizidine alkaloid, monocrotaline. In Adv. Exp. Med. Biol., “Taurine3: Cellular and Regulatory Mechanisms”, Schaffer, S., Lombardini, J.B. and Huxtable, R.J., eds., Plenum Press, New York, 442:85–89.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Jang-Yen Wu
    • 1
    • 2
  • Weiqing Chen
    • 1
  • Xiao Wen Tang
    • 1
  • Hong Jin
    • 1
  • Todd Foos
    • 1
  • John V. Schloss
    • 3
  • Kathleen Davis
    • 1
  • Morris D. Faiman
    • 4
  • Che-Chang Hsu
    • 1
  1. 1.Dept. of Mol. Biosci.Univ. of KansasLawrenceUSA
  2. 2.Inst. ofBiol. Chem.Academia SinicaTaipeiTaiwan
  3. 3.Dept. of Med. Chem.Univ. of KansasLawrenceUSA
  4. 4.Dept. of Pharmacol. & Toxicol.Univ. of KansasLawrenceUSA

Personalised recommendations