NMDA receptors stimulation

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

Horrocks, L. A. and Farooqui, A. A. NMDA receptor-stimulated release of arachidonic acid mechanisms for the Bazan effect. In Municio, A. M. and Miras-Portugal, M. T. (eds), Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease. New York Plenum Press, 1994, pp. 113-128. 

Pancreatic beta cells in rats express NMDA receptors, stimulation of which leads to insulin secretion (325). The authors postulated that dextromethorphan inhibits insulin secretion by blocking NMDA receptors and thus impairs glucose tolerance. Both patients had reduced insulin... 

Fink K, Bonisch H, Gothert M (1990) Presynaptic NMDA receptors stimulate noradrenaline release in the cerebral cortex. Eur I Pharmacol 185 115-17 Fink K, Schultheiss R, Gothert M (1992) Stimulation of noradrenaline release in human cerebral cortex mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Br I Pharmacol... 

Nakai, M., Qin, Z., Wang, Y., and Chase, T. N. (2000). NMDA and non-NMDA receptor-stimulated IkappaB-alpha degradation Differential effects of the caspase-3 inhibitor DEVD.CHO, ethanol and free radical scavenger OPC-14117. Brain Res. 859, 207-216. 

Because glutamate acting via NMDA receptors stimulates NO formation, it would be logical to expect that NOS neurons would be the first cells to succumb to excess NMDA receptor stimulation. However, NOS neurons are resistant to NMDA and NO neurotoxicity (Dawson and Snyder, 1994). It is unknown why NOS neurons are resistant to NMDA and NO neurotoxicity, but they probably possess protective factors that render them relatively resistant to the toxic NO environment they create. NOS neurons within the striatum are enriched in manganese SOD, and SOD in these neurons may... 

Neurological Mutations in SOD 1 result in human ALS and transgenic animal models rescued by antioxidants. NMDA-receptor stimulation produces superoxide. Defects in the function of complex 1 seen in Parkinson s disease. Vitamin E not protective in early Parkinson s disease. Vitamin E beneficial in Alzheimer s disease. A-acetylcysteine does not effect survival in ALS. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

There are important inhibitory systems built into the control of events following C-fibre stimulation. Thus, during peripheral noxious stimulation, spinal mechanism, driven by NMDA-receptor-mediated activity, can become active to damp down further neuronal responses, the purine, adenosine (see Chapter 13), appears to be involved in this type of control and has been reported to be effective in humans with neuropathic pain. It is thought that the depolarisations caused by activation of the NMDA receptor increase the metabolic demand on neurons and so ATP utilisation increases. ATP then is metabolised to adenosene and the purine then acts on its inhibitory Ai receptor in the... 

Status epilepticus occurs because the brain fails to stop an isolated seizure. The exact reason for this failure is unknown and probably involves many mechanisms. A seizure is likely to occur due to a mismatch of excitatory and inhibitory neurotransmitters in the brain. The primary excitatory neurotransmitter in the brain is glutamate. Glutamate stimulates postsynaptic N-methyl-D-aspartate (NMDA) receptors in the brain, causing an influx of calcium into the cells and depolarization of the neuron. Sustained depolarization may maintain SE and eventually cause neuronal injury and death.7 The primary... 

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