Glutamate receptors elevated levels

Galantamine is a ChE inhibitor, which elevates acetylcholine in the cerebral cortex by slowing the degradation of acetylcholine.37 It also modulates the nicotinic acetylcholine receptors to increase acetylcholine from surviving presynaptic nerve terminals. In addition, it may increase glutamate and serotonin levels. The clinical benefit of action of these additional neurotransmitters is unknown. 

Pathological activation of glutamate receptors is a common feature and one of the primary causes of neuronal death in acute neuronal injury (such as trauma, epilepsy, and brain ischemia) and chronic neurodegenerative diseases (such as Parkinson s disease, Alzheimer diseases, amyotrophic lateral sclerosis, and AIDS dementia) (Choi, 1988 Doble, 1999 Lipton and Rosemberg, 1994). In particular, elevation of extracellular glutamate level is a key factor in the development of neuronal damage under ischemic conditions. 

Fig. 10 Model of glutamate receptor Internalization through Ap-mediated activation of STEP. Ap activates the a7 nicotinic receptor, leading to Ca + influx and activation of calcineurin [197], Calcineurin subsequently dephosphorylates and activates STEP. Concomitantly, Ap also elevates STEP protein levels through inhibition of the ubiquitin proteasome system [203]. STEP dephosphorylates a regulatory tyrosine residue in both the NR2B and GluR2 glutamate receptor subunits, leading to internalization of the receptors [199,200]. As a result, synaptic function is disrupted (Figure from ref. 131, with permission)...

There is considerable evidence that overstimulation of glutamate receptors promotes cell death in a number of retinal disease processes. Glutamate overstimulation may be particularly important in acute ischemic injuries, but it also may play a role in diabetic retinopathy (16) and chronic neurodegenerative processes such as glaucoma (17). Evidence for this includes the observation that glutamate levels are elevated in the vitreous of patients with these conditions (16,17). 

High concentration of extracellular potassium (50 mM), which results in cellular depolarization, decreases NGF production by 30% in explanted rat iris (Hellweg et al., 1988). In contrast, elevated potassium levels increase the concentration of rjjRNANGF jjj cultured hippocampal neurons (2 fra et al., 1990). Depolarization produced by electrolytic lesions or systemic intraventricular administration of glutamate receptor agonists produces a rapid rise in mRNA p in vivo (Gall and Isackson, 1989 Zafra et al., 1990 Gall et al., 1991). 

MacLean DA, Sinoway LI, Leuenberger U (1998) Systemic hypoxia elevates skeletal muscle interstitial adenosine levels in humans. Circulation 98 1990-2 Marchi M, Raiteri L, Risso F et al (2002) Effects of adenosine A and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes. Br J Pharmacol 136 434 10... 

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