Glutamate turnover

There is an emerging literature in MRS in adults with BD, with reports of decreases in dorsolateral prefrontal cortex of neuronal marker NAA (Winsberg et al., 2000) and abnormalities in phopholipid metabolism (Kato et ah, 1995, 1998 Hamakawa et ah, 1999). There is preliminary work to suggest that cortical GABA levels and glutamate turnover are decreased in unipolar depression in adults, but these abnormalities may not be present in bipolar depression (Sanacora et al., 1999, Mason et al., 2000). 

Neurotransmitter turnover differs for the individual neurotransmitters. Glutamate and glycine require... 

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

Jabaudon D, Shimamoto K, Yasuda-Kamatani Y, Scanziani M, GahwEer BH, et al. 1999. Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin. Proc Natl Acad Sci U S A 96(15) 8733-8738. 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

Davis M, Myers KM (2002) The role of glutamate and gamma-aminobutyric acid in fear extinction clinical implications for exposme therapy. Biol Psychiatry 52 998-1007 Davis M, Whalen PJ (2001) The amygdala vigilance and emotion. Mol Psychiatry 6 13-34 Davis M, Hitchcock JM, Bowers MB, Berridge CW, Meha KR, Roth RH (1994) Stress-induced activation of prefrontal cortex dopamine turnover blockade by lesions of the amygdala. Brain Res 664 207-210... 

Nicolle M. M., Colombo P. J., Gallagher M., and McKinney M. (1999). Metabotropic glutamate receptor-mediated hippocampal phosphoinositide turnover is blunted in spatial learning-impaired aged rats. J. Neurosci. 19 9604-9610. 

Dopamine induces biochemical and physiological effects in the mammalian neostriatum. The occurrence of a D-l dopamine receptor (in the classification scheme of Kebabian and Caine) accounts for the ability of dopamine to enhance cyclic AMP formation. The occurrence of a D-2 dopamine receptor accounts for the ability of dopamine to inhibit cyclic AMP formation brought about by stimulation of a D-l dopamine receptor. Dopamine receptors mediate the regulation of (1) the release or turnover of acetylcholine (postsynaptic dopamine receptor) and (2) the release or turnover of dopar mine (presynaptic autoreceptor). Both receptors can be classified as D-2 dopamine receptors. Indications for the occurrence of dopamine receptors affecting the release or turnover of GABA, glutamate, serotonin and several neuropeptides are evaluated. 

A Postsynaptic Dopamine Receptor Regulating the Release or Turnover of Glutamate ... 

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