- Open Access
Role of taurine in the central nervous system
© Wu et al; licensee BioMed Central Ltd. 2010
- Published: 24 August 2010
Taurine demonstrates multiple cellular functions including a central role as a neurotransmitter, as a trophic factor in CNS development, in maintaining the structural integrity of the membrane, in regulating calcium transport and homeostasis, as an osmolyte, as a neuromodulator and as a neuroprotectant. The neurotransmitter properties of taurine are illustrated by its ability to elicit neuronal hyperpolarization, the presence of specific taurine synthesizing enzyme and receptors in the CNS and the presence of a taurine transporter system. Taurine exerts its neuroprotective functions against the glutamate induced excitotoxicity by reducing the glutamate-induced increase of intracellular calcium level, by shifting the ratio of Bcl-2 and Bad ratio in favor of cell survival and by reducing the ER stress. The presence of metabotropic taurine receptors which are negatively coupled to phospholipase C (PLC) signaling pathway through inhibitory G proteins is proposed, and the evidence supporting this notion is also presented.
- Endoplasmic Reticulum Stress
- GABAB Receptor
- Mammalian Central Nervous System
- Taurine Transporter
Taurine, 2-amino-ethanesulfonic acid, is one of the most abundant amino acids in mammals . The physiological role of taurine has received considerable attention since the reports that cats fed a taurine deficient diet developed central retinal degeneration  and cardiomyopathy . Now, taurine has been shown to be involved in many important physiological functions [for review, see ] e.g., as a trophic factor in the development of the CNS  and, for instance, kittens from the taurine-depleted mothers exhibit a delay in the migration of cells in the cerebellum and in the visual cortex . It also serves in maintaining the structural integrity of the membrane , regulating calcium binding and transport [7, 8], as an osmolyte [9, 10], a neuromodulator , a neurotransmitter [12–18] and a neuroprotector against L-glutamate (L-Glu)-induced neurotoxicity [19, 20]. In this article, the role of taurine in the central nervous system (CNS) as a neurotransmitter, a neuro-protective agent and a potent regulator for intracellular calcium homeostasis will be reviewed.
Taurine as a neurotransmitter
In general, a substance can be accepted as a neurotransmitter if it has fulfilled the following set of criteria: firstly, the substance and/or its synthesizing enzyme has to be present in the suspected neuron, preferably it is concentrated at the nerve terminal; secondly, it is released upon stimulation in a calcium-dependent manner; thirdly, it elicits proper physiological response; fourthly, a specific receptor is present and fifthly, an inactivation mechanism is present to terminate the action of the suspected neurotransmitter. The following lines of evidence have supported the notion that taurine is a neurotransmitter in the mammalian CNS: 1. The presence of a specific enzyme responsible for taurine biosynthesis in the brain, namely, cysteic/cysteine sulfinic acid decarboxylase (CAD/CSAD) which is distinctly different from the GABA-synthesizing enzyme, L-glutamate decarboxylase (GAD) was reported [21, 22]. Immunocytochemical studies have revealed the localization of CAD/CSAD in the cell body, dendrite as well as in the nerve terminal [24–26]; 2. Release of taurine has been shown to be either calcium dependent or calcium independent ; 3. Taurine has been shown to elicit neuronal hyperpolarization presumably through its action by opening the chloride channels in the cerebellum  and in the hippocampus ; 4. The presence of a specific taurine receptor has been demonstrated. Previously we reported the presence of specific taurine receptors which have Kd in nM range and are distinctly different from GABAA, GABAB and glycine receptors since the agonists or antagonists of these receptors have little effect on the binding of taurine to taurine receptors . Similar observations were recently reported by Frosini et al ; 5. The presence of a taurine transporter system for inactivation of its function has also been reported . In fact, taurine transporters have been cloned  and taurine transporter knock-out transgenic mice have been established . In summary, taurine has fulfilled most if not all of the criteria to be accepted as a neurotransmitter in the mammalian CNS.
Regulation of intracellular calcium homeostasis
Taurine as a neuroprotective agent
Taurine reduces glutamate-induced elevation of [Ca2+]I by inhibiting calcium influx from various calcium channels including the reverse mode of Na+/Ca2+ exchanger, various voltage-gated calcium channels (VGCC) such as L-, N- and P/Q-type, and glutamate NMDA receptors.
Taurine inhibits phosphorylation of VGCC resulting in decrease of calcium influx 3. Taurine also reduces the release of calcium from the internal storage pools presumably due to inhibition of phospholipase C.
Taurine inhibits glutamate-induced activation of calpain and the subsequent hetero-dimerization of Bcl-2 and Bax protein resulting in inhibition of release of cytochrome C and the apoptosis cascade (Fig 3).
This article has been published as part as part of Journal of Biomedical Science Volume 17 Supplement 1, 2010: Proceedings of the 17th International Meeting of Taurine. The full contents of the supplement are available online at http://www.jbiomedsci.com/supplements/17/S1.
- Jacobsen JG, Smith LH: Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev. 1968, 48: 424-511.PubMedGoogle Scholar
- Hayes KC, Carey RE, Schmidt SY: Retinal degeneration associated with taurine deficiency in the cat. Science. 1975, 188: 949-951. 10.1126/science.1138364.View ArticlePubMedGoogle Scholar
- Pion PD, Kittleson MD, Rogers QR, Morris JG: Myocardial failure in cats associated with low plasma taurine: A reversible cardiomyopathy. Science. 1987, 237: 764-768. 10.1126/science.3616607.View ArticlePubMedGoogle Scholar
- Huxtable RJ: Expanding the circle 1975-1999: sulfur biochemistry and insights on the biological functions of taurine. Adv Exp Med Biol. 2000, 483: 1-25. full_text.View ArticlePubMedGoogle Scholar
- Sturman JA: Taurine in development. Physiol Rev. 1993, 73: 119-147.PubMedGoogle Scholar
- Moran J, Salazar P, Pasantes-Morales H: Effect of tocopherol and taurine on membrane fluidity of retinal rod outer segments. Experimental Eye Research. 1988, 45: 769-776. 10.1016/S0014-4835(87)80094-5.View ArticleGoogle Scholar
- Lazarewicz JW, Noremberg K, Lehmann A, Hamberger A: Effects of taurine on calcium binding and accumulation in rabbit hippocampal and cortical synaptosomes. Neurochem Int. 1985, 7: 421-428. 10.1016/0197-0186(85)90164-0.View ArticlePubMedGoogle Scholar
- Lombardini JB: Effects of taurine on calcium ion uptake and protein phosphorylation in rat retinal membrane preparations. J Neurochem. 1985, 45: 268-275. 10.1111/j.1471-4159.1985.tb05503.x.View ArticlePubMedGoogle Scholar
- Solia JM, Herranz AS, Herreras O, Lerma J, Del Rio RM: Does taurine act as an osmoregulatory substance in the rat brain. Neurosci Lett. 1988, 91: 53-58. 10.1016/0304-3940(88)90248-0.View ArticleGoogle Scholar
- Wade JV, Olson JP, Samson FE, Nelson SR, Pazdernik TL: A possible role for taurine in osmoregulation within the brain. J Neurochem. 1988, 51: 740-745. 10.1111/j.1471-4159.1988.tb01807.x.View ArticlePubMedGoogle Scholar
- Kuriyama K: Taurine as a neuromodulator. Fed Proc. 1980, 39: 2680-2684.PubMedGoogle Scholar
- Okamoto K, Kimura H, Sakai Y: 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. 1983, 265 (1): 163-168. 10.1016/0006-8993(83)91350-1.View ArticlePubMedGoogle Scholar
- Lin C-T, Su YT, Song G-X, Wu J-Y: Is taurine a neurotransmitter in rabbit retina?. Brain Res. 1985, 337: 293-298. 10.1016/0006-8993(85)90066-6.View ArticlePubMedGoogle Scholar
- Taber TC, Lin C-T, Song G-X, Thalman RH, Wu JY: Taurine in the rat hippocampus-localization and postsynaptic action. Brain Res. 1986, 386: 113-121. 10.1016/0006-8993(86)90147-2.View ArticlePubMedGoogle Scholar
- Cunningham R, Miller RF: Taurine: Its selective action on neuronal pathways in the rabbit retina. Brain Res. 1976, 117: 341-345. 10.1016/0006-8993(76)90744-7.View ArticlePubMedGoogle Scholar
- Mandel P, Pasantes-Morales H, Urban PF: Taurine, a putative transmitter in retina. Transmitters in the Visual Process. Edited by: Bontig SL. 1976, Oxford: Pergamon, Oxford, 89-105.View ArticleGoogle Scholar
- Lin C-T, Li H-Z, Wu J-Y: Immunocytochemical localization of L-glutamate decarboxylase, gamma aminobutyric acid transaminase, cysteine-sulfinic acid decarboxylase, aspartate aminotransferase and somatostatin in rat retina. Brain Res. 1983, 270: 273-283. 10.1016/0006-8993(83)90601-7.View ArticlePubMedGoogle Scholar
- Lin C-T, Song G-X, Wu J-Y: Ultrastructural demonstration of L-glutamate decarboxylase and cysteinesulfinic acid decarboxylase in rat retina by immunocytochemistry. Brain Res. 1985, 331: 71-80. 10.1016/0006-8993(85)90716-4.View ArticlePubMedGoogle Scholar
- Tang XW, Deupree DL, Sun Y, Wu J-Y: Biphasic effect of taurine on excitatory amino acid-induced neurotoxicity. Taurine: Basic and Clinical Aspects. Edited by: R. J. Huxtable RJ, Azuma J, Nakagawa M, Kuriyama K, Bala A. 1996, New York: Plenum Publishing Co., 499-506.View ArticleGoogle Scholar
- El Edrissi A, Trenkner E: Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci. 1999, 19: 9459-9468.Google Scholar
- Wu J-Y, Moss LG, Chen MS: Tissue and regional distribution of cysteic acid decarboxylase in bovine brain. A new assay method. Neurochem Res. 1979, 4: 201-212. 10.1007/BF00964144.View ArticlePubMedGoogle Scholar
- Wu J-Y: Purification and characterization of cysteic/cysteine sulfinic acids decarboxylase and L-glutamate decarboxylase in bovine brain. Proc Natl Acad Sci USA. 1982, 79: 4270-4274. 10.1073/pnas.79.14.4270.PubMed CentralView ArticlePubMedGoogle Scholar
- Chan-Palay V, Lin CT, Palay S, Yamamoto M, Wu J-Y: 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. 1982, 79: 2695-2699. 10.1073/pnas.79.8.2695.PubMed CentralView ArticlePubMedGoogle Scholar
- Chan-Palay V, Palay SL, Li C, Wu J-Y: 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. 1982, 79: 4221-4225. 10.1073/pnas.79.13.4221.PubMed CentralView ArticlePubMedGoogle Scholar
- Magnusson KR, Madl JE, Clements JR, Wu J-Y, Larson AA, Beitz AJ: 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. 1988, 8 (12): 4551-4564.PubMedGoogle Scholar
- Magnusson KR, Clements JR, Wu J-Y, Beitz AJ: Co-localization of taurine- and cysteine sulfinic acid decarboxylase-like immunoreactivity in the hippocampus of the rat. Synapse. 1989, 4: 55-69. 10.1002/syn.890040107.View ArticlePubMedGoogle Scholar
- Okamoto K, Kimura H, Sakai Y: Taurine-induced increase of the Cl-conductance of cerebellar Purkinje cell dendrites in vitro. Brain Res. 1983, 259 (2): 319-323. 10.1016/0006-8993(83)91266-0.View ArticlePubMedGoogle Scholar
- Wu J-Y, Tang XW, Tsai WH: Taurine receptor: kinetic analysis and pharmacological studies. Adv Exp Med Biol. 1992, 315: 263-268.View ArticlePubMedGoogle Scholar
- Frosini M, Sesti C, Saponara S, Ricci L, Valoti M, Palmi M, Machetti F, Sgaragli G: A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation. Br J Pharmacol. 2003, 139: 487-494. 10.1038/sj.bjp.0705274.PubMed CentralView ArticlePubMedGoogle Scholar
- Chesney RW, Zelikovic I, Jones DP, Budreau A, Jolly K: The renal transport of taurine and the regulation of renal sodium-chloride-dependent transporter activity. Pediatr Nephrol. 1990, 4 (4): 399-407. 10.1007/BF00862526.View ArticlePubMedGoogle Scholar
- Han X, Budreau AM, Chesney RW: Molecular cloning and functional expression of an LLC-PK1 cell taurine transporter that is adaptively regulated by taurine. Adv Exp Med Biol. 1998, 442: 261-268.View ArticlePubMedGoogle Scholar
- Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Mönnighoff I, Buchczyk D, Donner M, Flögel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Häussinger D: Chronic liver disease is triggered by taurine transporter knockout in the mouse. FASEB J. 2006, 20 (3): 574-576.PubMedGoogle Scholar
- Chen WQ, Nguyen M, Carr J, Lee YJ, Jin H, Foos T, Hsu CC, Davis KM, Schloss JV, Wu J-Y: Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons. J Neurosci Res. 2001, 66: 612-619. 10.1002/jnr.10027.View ArticlePubMedGoogle Scholar
- Takuma K, Matsuda T, Hashimoto H, Asano S, Baba A: Cultured rat astrocytes possess Na+-Ca2+ exchanger. Glia. 1994, 12: 336-342. 10.1002/glia.440120410.View ArticlePubMedGoogle Scholar
- Schaffer S, Azuma J, Takahashi K, Mozaffari M: Why is taurine cytoprotective?. Taurine 5. Edited by: Lombardini J B, Schaffer S, Azuma J. 2003, London: Kluwer Academic/Plenum Publishers, 307-321.View ArticleGoogle Scholar
- Hamaguchi T, Azuma J, Schaffer S: Interaction of taurine with methionine: inhibition of myocardial phospholipids methyltransferase. J Cardiovasc Pharmacol. 1991, 18: 224-230. 10.1097/00005344-199108000-00008.View ArticlePubMedGoogle Scholar
- Chen WQ: Mode of action of taurine. Ph.D. dissertation. 2000, University of KansasGoogle Scholar
- Leon R, Wu H, Jin Y, Wei J, Buddhala C, Prentice H, Wu JY: Protective function of taurine in glutamate-induced apoptosis in cultured neurons. J Neurosci Res. 2009, 87 (5): 1185-1194. 10.1002/jnr.21926.View ArticlePubMedGoogle Scholar
- Schaffer S, Takahashi K, Azuma J: Role of osmoregulation in the actions of taurine. Amino Acids. 2000, 19: 527-546. 10.1007/s007260070004.View ArticlePubMedGoogle Scholar
- Kaczmarek LK: Phorbol esters, protein phosphorylation and the regulation of neuronal ion channels. J Exp Biol. 1986, 124: 375-392.PubMedGoogle Scholar
- Tang XW, Hsu CC, Schloss JV, Faiman MD, Wu E, Yang C-Y, Wu J-Y: Protein phosphorylation and taurine biosynthesis in vivo and in vitro. J Neuroscience. 1997, 17: 6947-6951.PubMedGoogle Scholar
- Wu J-Y, Tang XW, Tsai WH: Taurine receptor: Kinetic analysis and pharmacological studies. Taurine: Nutritional Value and Mechanisms of Action. Edited by: Lombardini JB, Schaffer SW, Azuma J. 1992, New York: Plenum Publishing Co., 263-268.View ArticleGoogle Scholar
- Foos TM, Wu J-Y: The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis. Neurochem Res. 2002, 27: 21-26. 10.1023/A:1014890219513.View ArticlePubMedGoogle Scholar
- Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B: Expression cloning of GABAB receptors undercovers similarity to metabotropic glutamate receptors. Nature. 1997, 386: 239-246. 10.1038/386239a0.View ArticlePubMedGoogle Scholar
- Lee YY, Deupree DL, Chen SC, Kao LS, Wu J-Y: Role of Ca2+ in AMPA mediated poly phosphoinositides turnover in primary neuronal cultures. J Neurochem. 1994, 62: 2325-2332. 10.1046/j.1471-4159.1994.62062325.x.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.