Modulation of taurine release by glutamate receptors and nitric oxide
Introduction
Taurine (2-aminoethanesulfonic acid) is a phylogenetically ancient molecule and an almost ubiquitous cellular constituent throughout the animal kingdom (Huxtable, 1992). It is also one of the most abundant free amino acids in the brain. The concentration of taurine in the central nervous system (CNS) even exceeds that of glutamate during the ontogenic development of many mammals (Oja and Kontro, 1983). This simple sulfonic acid has been shown to be an essential nutrient for cats, and probably also for primates, especially during development (Sturman, 1993), an observation which has given impetus to taurine supplementation of infant formulas derived from taurine-poor cow milk. Taurine is known to act as an osmoregulator in marine animals (Simpson et al., 1959) and has also been considered to function in the same role in the brains of terrestrial species (Walz and Allen, 1987). On the other hand, taurine induces hyperpolarization and inhibits firing of central neurons and has been thought to act as a modulator of synaptic activity in the brain (Oja et al., 1977, Oja and Kontro, 1983, Saransaari and Oja, 1992).
Taurine differs from most other amino acids in being a sulfonic acid and a β-amino acid. The sulfonate group is a strong acid which renders taurine almost completely zwitterionic in the physiological pH range. For this reason taurine is highly water- and poorly lipid-soluble, which effectively hampers its diffusion through lipophilic membranes. The relatively voluminous sulfonyl group is apparently likewise a pure mechanical hindrance to diffusion. The saturable carrier-mediated Na+-dependent uptake mechanisms (Kontro and Oja, 1978a, Kontro and Oja, 1978b, Oja and Kontro, 1983) are therefore able to maintain relatively high taurine concentration gradients across plasma membranes also in neural cells (Huxtable, 1989), even though in microdialysis studies in vivo relatively high extracellular levels of taurine are encountered under certain experimental conditions (Lerma et al., 1986). The properties of taurine release in an experimental model, brain slices, and the pertinent literature with a comparison to γ-aminobutyrate (GABA) release were reviewed by the present authors in this series less than a decade ago (Saransaari and Oja, 1992). The reader is referred to this article with respect to an exhaustive review of the early studies on taurine release from brain slices in vitro.
We now update present knowledge of taurine release and focus on the interactions of glutamate receptors and nitric oxide (NO) in the release. Glutamate is the major excitatory transmitter in the CNS. Extracellular excitatory amino acids are neurotoxic in excess and the resulting overstimulation of their receptors contributes to neuronal death in certain neurological diseases and in ischemia. Massive release of excitatory amino acids from neural structures during ischemia and hypoxia has indeed been observed both in vitro (Pellegrini-Giampietro et al., 1990, Collard and Menon-Johansson, 1990, Ohkuma et al., 1995) and in vivo (Benveniste et al., 1984, Hagberg et al., 1985, Globus et al., 1988). On the other hand, the agonists of glutamate receptors have also been shown to evoke taurine release from cerebral cortical and hippocampal slices (Saransaari and Oja, 1991, Saransaari and Oja, 1997b). Taurine is able to protect neurons against the excitotoxicity evoked by glutamate and its congeners (French et al., 1986, Trenkner, 1990, Tang et al., 1986) and prevent harmful metabolic cascades induced by ischemia or hypoxia (Schurr et al., 1987). The interactions of glutamate receptors with taurine release are thus potentially of great functional significance.
Furthermore, glutamate receptors can foment the production of NO, a short-lived synaptic messenger in the CNS. NO is a Janus-faced compound in the nervous system, exhibiting both beneficial and detrimental properties which have not yet been fully explored and understood.
Section snippets
General properties of taurine release
The release of taurine from neural tissue could be mediated by several possible mechanisms, including simple physical diffusion, penetration through membrane channels, carrier-mediated transport and exocytosis of vesicular taurine from nerve endings. Diffusion through cell plasma membranes is a pure physical phenomenon driven by the transmembrane concentration gradients, affected by the physicochemical properties of membranes and exhibiting non-saturable kinetics of transfer. Penetration
Glutamate receptors
Glutamate receptors belong to two main groups, ionotropic and metabotropic. Within these two groups the receptors are divided into different classes. The ionotropic receptors (iGluRs) contain cation-specific channels and are pharmacologically classified as N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Five subunits, NR1 and NR2A-D, have been isolated for NMDA receptors, five, GluR5-7 and KA1-2, for kainate receptors and four,
Nitric oxide
Nitric oxide (NO) is relatively recently discovered biological messenger (Moncada et al., 1991). It is a strange molecule to function in this role in the CNS. NO is a volatile and toxic gas, not stored in synaptic vesicles and not released upon exocytosis. It crosses biological membranes by diffusion, easily enters neural cells and instead of having specific membrane-bound receptors it acts directly on intracellular components. Its actions are terminated by neither active reuptake nor enzymatic
Effects of NMDA receptors
The presynaptic glutamate receptors have been demonstrated to regulate the release of transmitters in the hippocampus in vitro, e.g., that of glutamate (Smirnova et al., 1993), noradrenaline (Pittaluga and Raiteri, 1992) and GABA (Janáky et al., 1993). The release of β-alanine is likewise enhanced by glutamate receptor agonists in hippocampal slices from developing, but not from adult mice (Saransaari and Oja, 1999a). In most investigations glutamate and glutamate agonists have also been shown
Glutamate receptor effects
The interactions of glutamatergic compounds with the release of taurine in vivo have been studied mainly in the striatum or hippocampus. In the striatum corticostriatal glutamatergic pathways terminate at GABA projection neurons and interneurons (Kita, 1993). Furthermore, GABA projection neurons have been shown to contain taurine (Palkovits et al., 1986, Smith and Bolam, 1990), which is enriched in synaptosomes and synaptic vesicle fractions (Kontro et al., 1980). In the hippocampus glutamate
Conclusions
Results from studies in vitro and in vivo on adult animals are in general in concert with each other, but the regulation of taurine release by glutamate receptors and NO seems to be somewhat different in mature and immature nervous tissues. The release of taurine from the brain is enhanced by glutamate receptor agonists. This enhancement is inhibited by the respective receptor antagonists both in vitro and in vivo. The ionotropic NMDA and AMPA receptor agonists seem to be the most effective in
Acknowledgements
The technical assistance of Mrs Sari Luokkala and the financial support of the Medical Research Fund of Tampere University Hospital and the Academy of Finland are gratefully acknowledged.
References (191)
- et al.
Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction
J. Biol. Chem.
(1992) - et al.
In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats
Neurosci. Lett.
(1997) - et al.
Kainic acid syndrome and binding sites in developing rats
Dev. Brain Res.
(1984) - et al.
The release of amino acids from rat neostriatum and substantia nigra in vivo. A dual microdialysis probe analysis
Neuroscience
(1998) - et al.
Possible involvement of nitric oxide in long-term potentiation
Eur. J. Pharmac.
(1991) - et al.
Group I metabotropic glutamate receptors: implications for brain diseases
Prog. Neurobiol.
(1999) - et al.
Characteristics of nitric oxide-evoked []taurine release from cerebral cortical neurons
Neurochem. Int.
(1996) - et al.
Nitric oxide actions in neurochemistry
Neurochem. Int.
(1996) - et al.
Hydroxylamine is a vasorelaxant and a possible intermediate in the oxidative conversion of L-arginine to nitric oxide
Biochem. Biophys. Res. Commun.
(1989) - et al.
Metabotropic glutamate receptor agonists inhibit endogenous glutamate release from rat striatal synaptosomes
Eur. J. Pharmac.
(1995)
In vivo studies of the cerebral glutamate receptor/NO/cGMP pathway
Progr. Neurobiol.
Differential expression of metabotropic glutamate receptors in the hippocampus and entorhinal cortex of the rat
Mol. Brain Res.
Alterations in excitatory and GABAergic inhibitory connections in hippocampal transplants
Neuroscience
In vivo elevation of extracellular potassium in the rat amygdala increases extracellular glutamate and aspartate and damages neurons
Neuroscience
Glutamate, nitric oxide and cell–cell signalling in the nervous system
Trends Neurosci.
Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely moving rats in vivo
Brain Res.
Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia
Neurosci. Lett.
Release of taurine from cultured cerebellar granule cells and astrocytes: co-release with glutamate
Neuroscience
Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons
Brain Res.
Taurine in the central nervous system and the mammalian actions of taurine
Prog. Neurobiol.
Bright and dark sides of nitric oxide in ischemic brain injury
Trends Neurosci.
Nitric oxide mediates NMDA-evoked []GABA release from chick retina cells
FEBS Lett.
The ontogeny of excitatory amino acid receptors in the rat forebrain. I. N-Methyl-D-aspartate and quisqualate receptors
Neuroscience
Release of GABA from rat hippocampal slices: involvement of quisqualate/N-methyl-D-aspartate-gated ionophores and extracellular magnesium
Neuroscience
Ibotenate stimulates glutamate release from guinea pig cerebrocortical synaptosomes: inhibition by L-2-amino-4-phosphonobutyrate (L-AP4)
Neurosci. Lett.
No enhancement by nitric oxide of glutamate release from P2 and P3 synaptosomes of rat hippocampus
Brain Res.
Nitric oxide inhibition of the depolarization-evoked glutamate release from synaptosomes of rat cerebellum
Neurosci. Lett.
GABAergic circuits of the striatum
Prog. Brain Res.
Sodium dependence of taurine uptake in rat brain synaptosomes
Neuroscience
Free amino acids in the synaptosome and synaptic vesicle fractions of different bovine brain areas
Brain Res.
Spontaneous and depolarization-induced efflux of hypotaurine from mouse cerebral cortex slices: comparison with taurine and GABA
Life Sci.
L-Glutamate-induced swelling of cultured astrocytes is dependent on extracellular Ca2+
Neurosci. Lett.
Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex
Neuron
In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis
Brain Res.
The depolarization-induced outflow of D-[]-aspartate from rat brain slices is modulated by metabotropic glutamate receptors
Neurochem. Int.
Nitric oxide induces neurotransmitter release from hippocampal slices
Eur. J. Pharmac.
Differential effects of aging on binding sites of the activated NMDA receptor complex in mice
Mech. Ageing Dev.
Effects of aging on NMDA and MK-801 binding sites in mice
Brain Res.
Age-related changes in excitatory amino acid receptors in two mouse strains
Neurobiol. Aging
NMDA-, kainate-, and quisqualate-stimulated release of taurine from electrophysiologically monitored rat hippocampal slices
Brain Res.
Nitric oxide-induced blockade of NMDA receptors
Neuron
Cyanide selectively augments kainate- but not NMDA-induced release of glutamate and taurine
Eur. J. Pharmac.
Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat hippocampus
Exp. Neurol.
Extracellular taurine release in rat hippocampus evoked by specific glutamate receptor activation is related to the excitatory potency of glutamate agonists
Neurosci. Lett.
The ontogeny of excitatory amino acid receptors in the rat forebrain. II: Kainic acid receptors
Neuroscience
Involvement of nitric oxide in long-term potentiation in the dentate gyrus in vivo
Brain Res.
Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity
Neuron
Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders?
Trends Neurosci.
Nitric oxide-evoked []γ-aminobutyric acid release is mediated by two distinct release mechanisms
Mol. Brain Res.
Lamotrigine and carbamazepine affect differently the release of D []aspartate from mouse cerebral cortical slices: involvement of NO
Neurochem. Res.
Cited by (58)
Dietary sulfur amino acid modulations of taurine biosynthesis in juvenile turbot (Psetta maxima)
2013, AquacultureCitation Excerpt :Taurine concentration of the whole body remained static after methionine or cysteine supplementation, increased but to a much less extent than that in the liver by taurine supplementation. These results could be explained by the fact that taurine homeostasis in the body is maintained not only by synthesis, but also by many other factors, including transportation (Pinto et al., 2012), release (Oja and Saransaari, 2000), etc. Taurine is an important element for the growth of juvenile turbots, and the juvenile turbots are able to utilize crystalline taurine.
Stress during development alters anxiety-like behavior and hippocampal neurotransmission in male and female rats
2012, NeuropharmacologyCitation Excerpt :Interestingly, taurine interacts with GABA, competitively inhibiting [3H]muscimol binding to purified GABAA receptors (Bureau and Olsen, 1991), and it interacts with GABAA receptors linked to benzodiazepine binding sites, suggesting that it may have a modulatory role on GABA-benzodiazepine neurotransmission (Medina and De Robertis, 1984). In addition, taurine and GABA are released simultaneously with excitatory amino acids, limiting and preventing excitation from reaching neurotoxic levels (Albrecht and Schousboe, 2005), thus acting as a protective factor against the excitotoxicity evoked by excessive glutamate receptor activation (Oja and Saransaari, 2000). Notably, impairment of GABA neurotransmission is classically involved with anxiety-like behavior measured in numerous animal models such as the open-field and the zero maze in mice (Kash et al., 1999) and light–dark transition test (Stork et al., 2000), whereas agonists of the GABAA receptor and GABA mimetic drugs reduce anxious behavior in the elevated plus maze, particularly entries in the open arm and risk assessment (Corbett et al., 1991; Griebel et al., 1996; Rodgers et al., 1997).
Simultaneous quantification of d- vs. l-serine, taurine, kynurenate, phosphoethanolamine and diverse amino acids in frontocortical dialysates of freely-moving rats: Differential modulation by N-methyl-d-aspartate (NMDA) and other pharmacological agents
2011, Journal of Neuroscience MethodsCitation Excerpt :Confirmation of a specific role of NMDA receptors in its actions was shown by blockade of the NMDA-induced rise in taurine levels by pre-treatment with the competitive antagonist, CPP (20 mg/kg, s.c.). Increases in taurine levels by NMDA are likely, as evoked in the introduction, to influence neurotransmission (Oja and Saransaari, 2000; Albrecht and Schousboe, 2005; Wu and Prentice, 2010). Excitotoxic effects associated with pronounced activation of NMDA receptors will ultimately lead to cellular damage, as reflected in elevations in extracellular levels of PEA, an indicator of membrane integrity (Yao et al., 2000; Vance, 2008; Li et al., 2010), and CPP abrogated the increase in PEA levels elicited by NMDA, confirming the implication of NMDA receptors.
Protection by taurine of rat brain cortical slices against oxygen glucose deprivation- and reoxygenation-induced damage
2009, European Journal of Pharmacology