Effect of Systemic Administration of N‐Methyl‐d‐Aspartic Acid on Extracellular Taurine Level Measured by Microdialysis in the Hippocampal CA1 Field and Striatum of Rats

Abstract

The extracellular concentrations of amino acids in the hippocampal CA1 field and striatum of conscious freely moving rats were monitored simultaneously by in vivo brain microdialysis using HPLC with electrochemical detection. Under basal conditions, aspartate, glutamate, glutamine, glycine, taurine, and alanine were detected, but gamma-aminobutyric acid was undetectable in both regions. Intraperitoneal injection of N-methyl-D-aspartic acid (NMDA; 10 mg/kg) caused a significant increase (three- to fivefold) in the taurine concentration in the dialysate obtained from both the hippocampal CA1 and striatum, whereas other amino acids (aspartate, glutamate, and alanine) did not show significant changes. Local application of NMDA (300 microM) to both regions via the dialysis probes also caused a similar increase (three- to fivefold) in both regions. Under infusion of hypertonic Ringer's solution containing 150 mM sucrose, the effect of NMDA on the level of taurine in both the regional dialysates was not affected. The effect of NMDA was totally reduced by intraperitoneal administration of MK-801 (0.3-1.0 mg/kg), a noncompetitive antagonist of NMDA receptors. Continuous infusion of DL-2-amino-5-phosphonovaleric acid (1.0 mM), a competitive antagonist of NMDA receptors, via the dialysis probes completely inhibited the effect of NMDA. These findings suggest that systemic administration of NMDA is effective as well as local administration into the brain and that NMDA receptors might be involved in the regulation of the extracellular taurine level in the brain without dependence on cell swelling.

Serum Amino Acid Levels after Permanent Middle Cerebral Artery Occlusion in the Rat

“…Extracellular taurine increases on neural ischemic tissue have been described by microdialysis in experimental models of permanent [23, 26, 27, 44]or transient ischemia [27, 30, 45, 46, 47, 48, 49]. Taurine is believed to act as an inhibitory neurotransmitter [50, 51]or neuromodulator [52], and may counterbalance the excitotoxic action of glutamate and aspartate during cerebral ischemia, in particular the secondary effect of those amino acids on cell swelling by its osmoregulatory action [53]. In spite of the evidence previously referred to, we have found no changes in the levels of serum taurine in our experimental model of permanent MCAO; these results are in agreement with previous studies in which we also did not observe changes of this amino acid in plasma and CSF of patients with acute cerebral infarction [15], and with the absence of a change of taurine levels described in some microdialysis studies performed in experimental transient ischemia [54, 55].…”

Taurine Interaction with Neurotransmitter Receptors in the CNS: An Update

“…Wherever possible, the quantitative aspect will be critically addressed: the question is whether the quantities of taurine applied and/or present in the particular cell compartments in vivo or in vitro, are sufficient to subserve the putative function in situ. In this context it is important to note that extracellular taurine in the different brain regions as measured by microdialysis ranges from $1 to 10 lM in resting state and does not exceed 100--120 lM following depolarization or application of other release stimuli (15)(16)(17)(18)(19)(20)(21)(22).…”

Taurine Release by Astrocytes Modulates Osmosensitive Glycine Receptor Tone and Excitability in the Adult Supraoptic Nucleus

“…If this is the case, the excitatory effects of locally applied strychnine observed in this nucleus would have to be caused by a blockade of GlyRs on local interneurons, rather than those on VP neurons themselves. Another factor confounding the taurinergic gliotransmission hypothesis is that two other agonists of GlyRs, namely glycine and ␤-alanine (Mori et al, 2002;Lynch, 2004), are present in the extracellular fluid (Shibanoki et al, 1993), and it is not known whether GlyRs are functionally activated by taurine or these other molecules in situ. Finally, it is well known that both neurons and glial cells can potentially release taurine (Olson and Li, 2000), making it difficult to establish whether any observable GlyR tone is mediated specifically by an agonist released from glial cells.…”