Brain y-aminobutyrate

Asada, H, Kawamura, Y, Maruyama, K, Kume, H, Ding, RG, Kanbara, N, Kuzume, H, Sanbo, M, Yagi, T and Obata, K (1997) Cleft palate and decreased brain y-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. Proc. Natl. Acad. Sci. USA 94 6496-6499. 

Braestrup, C., Nielsen, E. B., Sonnewald, U., Knutsen, J. S., Andersen, K. E., Jansen, J. A., Erederiksen, K., Andersen, P. H., Mortnesen, A., Suzdak, P.D. (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-l-yl] nipecotic acid binds with high afhnity to the brain y-aminobutyric acid uptake carrier. J. Neuroehem. 

The 2-diazo-4-R-imidazoles (R = H, CH2COOH) showed sufficient stability in neutral medium to be tested in binding experiments for the rat brain y-aminobutyric acid (GABA) receptor (87JMC2222). They had an ICso of 5.10" M and 7.10 M, respectively, and they recognized the GABA receptor. Therefore they can be used as potential irreversible probes for this receptor. 

Nucleophilic groups from enzymes can add to double bonds, e.g., in an aminoacrylate Schiff base, or to multiple bonds present in die inhibitor. An example is y-vinyl y-aminobutyrate (4-amino-5-hexenoic acid), another inhibitor of brain y-aminobutyrate aminotransferase which is a useful anticonvulsant drug. 

Friedman SD, Baker LD, Borson S, Jensen JE, Bareness SM, Craft S et al (2013) Growth hormone-releasing hormone effects on brain y-aminobutyric acid levels in mild cognitive impairment and healthy aging. JAMA Neurol 70 883-890... 

Several amino-acids are important neurotransmitters in the c.n.s. Glutamic and aspartic acids seem to be excitatory transmitters in the entire brain. y-Aminobutyric acid (GABA) and glycine are important inhibitory transmitters, the former in supraspinal interneurons and the latter at spinal interneurons (Curtis and Johnston, 1970). Of the polypeptide neurotransmitters, the most studied have been the endorphins and enkephalins (see Section 12.8), Substance P (an undecapeptide that helps transmit the sense of pain (von Euler and Pernow, 1977, somatostatin, and gastrin, and cholecystokinin whose action in the gut has been well researched. For more on GABA, see Section 12.7. 

Strong acids or bases catalyze the hydrolysis of 2-pyrrohdinone to 4-aminobutanoic acid [y-aminobutyric acid [56-12-2] (GABA)]. GABA is involved in the functioning of the brain and nervous system and is of considerable interest as a potential dietary supplement (60). 

Martin, DF and Rim vail, K (1993) Regulation of y-aminobutyric acid S5mthesis in the brain. J. 

Mechanism of Action The mechanism of action of divalproex is not well understood. It is known to affect ion transport and enhances the activity of y-aminobutyric acid. Like lithium, it also has possible neuroprotective effects through enhancement of brain-derived neurotrophic factor.31... 

Van Gelder NM. A possible enzyme barrier for y-aminobutyric acid in the central nervous system. Prog Brain Res 1967 29 259-268. 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

High levels of homocysteine or one of its metabolites may directly affect brain function. The administration of homocysteine to rats induces grand mal convulsions, a phenomenon that is aggravated by either methionine or pyridoxine. Homocysteine-induced blockade of the y-aminobutyric acid (GABA) receptor may be involved. In addition, brain can oxidize homocysteine to homocys-teic acid, which has a glutamatergic activity. 

The CNS also contains a descending system for control of pain transmission. This system originates in the brain and can inhibit synaptic pain transmission at the dorsal horn. Important neurotransmitters here include endogenous opioids, serotonin, norepinephrine, y-aminobutyric acid, and neurotensin. 

Schwarzer, C., Berresheim, U Pirker, S Wieselthaler, A., Fuchs, K., Sieghart, W., and Sperk, G. (2001) Distribution of the major y-aminobutyric acidA receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat../. Comp. Neurol. 433,526-549. 

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