Glutamatergic neurotransmission

Although, to our knowledge, the effects of inhalation of amyl nitrite or butyl nitrite on glutamatergic neurotransmission have not been studied, NO, the potent compound that mediates the peripheral effects of nitrites in blood vessels, if released in the CNS when nitrites are inhaled, may potentially affect the glutamatergic system. NO has been reported to act directly on the postsynaptic NMDA receptor, where it can increase or decrease NMDA-mediated currents and subsequent calcium influx (Aizenman et al. 1990 Dingledine et al. 1999 Manzoni et al. 1992). 

Many sites within the pons and medulla that contribute to the increased levels of arousal that characterize wakefulness and rapid eye movement (REM) sleep are under glutamatergic control. The pontine reticular formation, for example, is involved in phenomena related to REM sleep and to motor activity during wakefulness. Glutamatergic neurotransmission also mediates the responses of cells of the medial pontine reticular formation. These cells are depolarized and... 

Feenstra, M.G., Botterblom, M.H., van Uum, J.F. Behavioral arousal and increased dopamine efflux after blockade of NMDA-receptors in the prefrontal cortex are dependent on activation of glutamatergic neurotransmission. Neuropharmacology. 42 752, 2002. 

Dent, J.A., Davis, M.W. and Avery, L. (1997) Avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBOJournal 16, 5867-5879. 

A growing body of evidence is emerging that suggests glutamatergic neurotransmission plays a key role in the etiology of the disease. 

Memantine (Namenda) blocks glutamatergic neurotransmission by antagonizing N-methyl-D-aspartate receptors, which may prevent excitotoxic reactions. It is used as monotherapy, and data suggest that when it is combined with a cholinesterase inhibitor, there is improvement in cognition and activities of daily living. 

In order to understand the hypothesis of excessive excitation of neurons by glutamate, it is necessary to understand glutamatergic neurotransmission. 

Martini LH, Jung F, Soares FA, Rotta LN, Vendite DA, Frizzo ME, Yunes RA, Calixto JB, Wofchuk S, Souza DO. 2007. Naturally occurring compounds affect glutamatergic neurotransmission in rat brain. Neurochem Res 32 1950-1956. 

Another mechanism of synaptic dysfunction in AD may involve amyloid ft peptide (Aft a 40 to 42 amino acid peptide). A marked increase in Aft levels occurs in brain tissue from AD patients. A ft inhibits glutamatergic neurotransmission and reduces synaptic plasticity (Snyder et al., 2005). Treatment of cortical neuronal cultures with Aft facilitates endocytosis of NMDA receptor. Aft-mediated endo-cytosis of NMDA receptor requires the a-1 nicotinic receptor, protein phosphatase 2B, and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyrl472 correlates with receptor endocytosis. The addition of a y-secretase inhibitor not only reduces Aft but also restores surface expression of NMDA receptors, suggesting that A plays an important role in the regulation of NMDA and AMPA receptor trafficking (Snyder et al., 2005 Morishita et al., 2005). 

The multitude of entries in Table 4 bears witness to an important impact of serotonin on glutamatergic neurotransmission. The predominant effect is inhibitory and... 

Tsai G, van Kammen DP, Chen S, Kelley ME, Grier A, et al. 1998. Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia. Biol Psychiatry 44 667-674. 

Price CJ, Pittman QJ (2001) Dopamine D4 receptor activation inhibits presynaptically glutamatergic neurotransmission in the rat supraoptic nucleus. J Neurophysiol 36 1149-1155. 

---