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.
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.
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