Neuropeptide Y release from cultured hippocampal neurons: stimulation by glutamate acting at N-methyl-d-aspartate and AMPA receptors

Neuroscience ◽  
1997 ◽  
Vol 81 (1) ◽  
pp. 23-31 ◽  
Author(s):  
A Gemignani ◽  
S Marchese ◽  
G Fontana ◽  
M Raiteri
Neuron ◽  
2001 ◽  
Vol 29 (1) ◽  
pp. 243-254 ◽  
Author(s):  
Wei-Yang Lu ◽  
Heng-Ye Man ◽  
William Ju ◽  
William S. Trimble ◽  
John F. MacDonald ◽  
...  

2001 ◽  
Vol 79 (5) ◽  
pp. 422-429 ◽  
Author(s):  
Samuel Toong ◽  
Zhi-Gang Xiong ◽  
Sergei I Zavorin ◽  
Donglin Bai ◽  
B A Orser ◽  
...  

Positive modulators of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) channels reduce desensitization and alter their gating kinetics. We have discovered a novel compound nitric oxide-mimetic that similarly modulates the AMPA receptor by reducing desensitization. This, designated GT-005, belongs to the organic nitrate family that includes the nitrovasodilator nitroglycerine. In acutely isolated hippocampal neurons, GT-005 enhanced kainate (100 µM)-evoked currents with an EC50 of 1.7 ± 0.2 mM and a 176 ± 10% maximal increase in the steady-state current response. Similar results were found in cultured hippocampal neurons (EC50 of 1.3 ± 0.2 mM and a maximal 83 ± 14% increase in the steady-state current response). GT-005 reduced the desensitization of glutamate-evoked currents and slowed the onset of desensitization. This compound also increased the rate of recovery from the desensitized state. With respect to alteration of the excitatory synaptic transmission, GT-005 delayed the decay and increased the frequency of spontaneous miniature excitatory postsynaptic currents (mepsc) recorded in cultured hippocampal neurons.Key words: AMPA receptors, desensitization, organic nitrates.


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