Amino acid microdialysis

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

Kodama, T., Lai, Y. Y. 8r Siegel, J. M. (2003). Changes in inhibitory amino acid release linked to pontine-induced atonia an in vivo microdialysis study. J. Neurosci 23, 1548-54. 

Klinker CC, Bowser MT (2007) 4-Fluoro-7-nitro-2, 1, 3-benzoxadiazole as a fluorogenic labeling reagent for the in vivo analysis of amino acid neurotransmitters using online microdialysis-capillary electrophoresis. Anal Chem 79 8747-8754... 

I thank Owen Parkes for editing the English text. This textbook is dedicated to two of my research colleagues at INSERM Unity 26. The first is Doctor Jeanne-Marie Lefauconnier who will retire in April 2002 after a long and fruitful career studying the amino acid transporters at the BBB. The second is Doctor Gaby Boschi, who died in October 2001. Her work has provided us with unique insights into the impact of brain microdialysis on neuropharmacokinetics. 

Parent M, Bush D, Rauw G, Master S, Vaccarino F, et al. 2001. Analysis of amino acids and catecholamines, 5-hydroytryp-tamine and their metabolites in brain areas in the rat using in vivo microdialysis. Methods 23 11-20. 

Bianchi L, Colivicchi MA, Bolam JP, Della Corte L. 1998. The release of amino acids from rat neostriatum and substantia nigra in vivo a dual microdialysis probe analysis. Neuroscience 87(1) 171-180. 

Kanthan R, Shuaib A. 1995. Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry 59(3) 326-327. 

Paulsen RE, Lonnum L. 1989. Role of glial cells for the basal and Ca " -dependent K" -evoked release of transmitter amino acids investigated by microdialysis. J Neurochem 52(6) 1823-1829. 

Silverstein FS, Naik B. 1991. Effect of depolarization on striatal amino acid efflux in perinatal rats an in vivo microdialysis study. Neurosci Lett 128(1) 133-136. 

Timmerman W, Cisci G, Nap A, de Vries JB, Westerink BH. 1999. Effects of handling on extracellular levels of glutamate and other amino acids in various areas of the brain measured by microdialysis. Brain Res 833(2) 150-160. 

Tossman U, Ungerstedt U. 1986. Microdialysis in the study of extracellular levels of amino acids in the rat brain. Acta Physiol Scand 128(1) 9-14. 

Zhou SY, Zuo H, Stobaugh JE, Lunte CE, Lunte SM. 1995. Continuous in vivo monitoring of amino acid neurotransmitters by microdialysis sampling with on-line derivatization and capillary electrophoresis separation. Anal Chem 67(3) 594-599. 

Kanthan R, Shuaib A (1995) Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry 59 326-327 Karcz-Kubicha M, Jessa M, Nazar M, et al (1997) Anxiolytic activity of glycine-B antagonists and partial agonists—no relation to intrinsic activity in the patch clamp. Neuropharmacology 36 1355-1367... 

Figure 27.17 Separation and determination of amino acids by reversed phase gradient LCEC of isoindole derivatives. The sample was obtained from an awake monkey using a microdialysis sampling probe to collect amino acids from the extracellular fluid of the brain.

Most electrode materials that are employed in LCEC can also be used for CEEC. The most commonly employed working electrode is a carbon fiber. Carbon fibers come in many different sizes and can also be etched to smaller diameters. Common applications of CEEC with carbon fiber electrodes are the detection of catecholamines in single neuronal cells and amino acids in brain microdialysis samples following derivatization with NDA/CN. 

Microdialysis experiments show that BEO (0.5 ml/kg) did not affect basal amino acid levels, whereas it significandy reduced the efflux of excitatory amino acid, namely aspartate and glutamate, in the frontoparietal cortex typically observed following MCAo (Fig. 2). Extracellular levels of glycine, GABA,... 

The excitotoxic index was developed by our group as a composite descriptor of excitatory/inhibitory amino acid neurotransmitter balance as measured by microdialysis in the brain s extracellular space (66,102). This index is defined as ... 

Kawamata T., Katayama Y., Hovda D. A., Yoshino A., and Becker D. P. (1992) Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J. Cereb. Blood Flow Metab. 12,12-24. 

De Lange ECM, De Boer AG, Breimer DD (2000) Methodological issues in microdialysis sampling for pharmacokinetic studies. Adv Drug Deliv Rev 45 125-148 Elmquist WF, Sawchuk RJ (1997) Application of microdialysis in pharmacokinetic studies. Pharm Res 14 267-288 Evrard PA, Deridder G, Verbeeck RK (1996) Intravenous microdialysis in the mouse and the rat development and pharmacokinetic application of a new probe. Pharm Res 13 12-17 Jacobson I, Sandberg M, Hamberger A (1985) Mass transfer in brain dialysis devices a new method for the estimation of extracellular amino acids concentration. J Neurosci Methods 15 263-268... 

Hamberger A, Jacobson I, Larsson S, Lonnroth P, Nystrom B, Sandberg M (1991) Microdialysis technique for studying brain amino acids in the extracellular fluid Basic and clinical studies. In Microdialysis in the Neurosciences. Techniques in the Behavioral and Neural Sciences, Vol. 7, TE Robinson and JB Justice Jr, Eds., pp. 407-423. Elsevier Sdence Publishers, Amsterdam. 

Also in the intact brain push pull cannula and microdialysis experiments have demonstrated K+-evoked Ca +-dependent Asp release from the striatum (Girault et al., 1986 Paulsen and Fonnum, 1989 but see Zuiderwijk et al., 1996). Recently Lada et al. (1998) demonstrated Ca -dependent release of Asp from the striatum after electrical stimulation of the prefrontal cortex. Experiments interfering with the exocytotic machinery have also been performed in the intact striatum. Analysis of microdialysates (Herrera-Marschitz et al., 1996) has shown that extracellular Asp levels were decreased during K+-induced depolarization after treatment with alpha-latrotoxin, which triggers sustained exocytosis (Henkel and Sankaranarayanan, 1999). This is presumably because of depletion of the vesicular content of Asp before the stimulated release. However, care should be taken in interpreting this result, because alpha-latrotoxin may release both vesicular and cytoplasmic pools of amino acids (McMahon et al., 1990). Nonetheless, most experiments in the intact brain, using both direct chemical depolarization of the tissue and stimulation of pathways, show Asp release consistent with exocytosis. 

A study by Rao et al." measured the levels of amino acids using in vivo cerebral microdialysis in the frontal cortex of portacaval-shunted rats administered ammonium acetate to precipitate severe portal-systemic encephalopathy. In comparison to sham-operated control rats, tryptophan levels increased by 63% along with those of other amino acids. However, the experimental animals did not have a significant increase in extracellular fluid concentration of tryptophan, suggesting that increased spontaneous release of tryptophan in cerebral cortex is not implicated in the pathogenesis of hepatic coma. 

Rao, V. L., Audet, R. M., and Butterworth, R. E., Selective alterations of extracellular brain amino acids in relation to function in experimental portal-systemic encephalopathy Results of an in vivo microdialysis study, ]. Neurochem., 65, 1221, 1995. 

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