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pure glycine excitatory receptors?

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As we all know (do we? do we?) NMDA type of glutamate receptors consists of two kinds of sites, NR1 (glycine binding site) and NR2 (glutamate binding site, subtypes NR2A-NR2D).

Now I came across this study:

Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.

If I understood it correctly, there are receptors that consist of NR1 and NR3 glycine binding sites, but no glutamate sites at all, and they perform an excitatory role. Am I right?

What I don't understand is this quote:

By itself, glycine is normally thought of as an inhibitory neurotransmitter.

After all, glycine stimulation of NR1 sites is required for the activation of an NMDA receptor, and NMDA receptors are excitatory. So what do they mean, other pure glycine receptors which don't form an NR1-NR3 complex, or...?


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confused, but interesting. i've been trying to figure out the implications of glutamate over-transmission, since i've read a lot of recently that seems to implicate that as the cause behind ocd.

mind unraveling the glutamate/nmda connection for those of us not quite caught up? or any of the other assumed points of knowledge, that might help others to understand what glycine is, and how it all interrelates?

doubt i can answer your question, but maybe you can educate a few others too.

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This article is just kind of odd.

My translation is that they found a new receptor that looks like normal NMDA receptors, except it ONLY accepts glycine and not aspartate/NMDA (so as you said). Also, normal NMDA blockers such as magnesium ions and diclozipine/MK-801 do not block it.

The weird thing they found is that serine inhibits it, even though serine activates normal NMDA receptor channels.

Perhaps it has a role in homeostasis of NMDA-like excitatory activity? I.e., an excess of serine for whatever reason will not cause an overexcitement in the brain? I.e. i.e., serine will simultaneously cause inhibitory and excitatory responses?

And in fact, since you state that glycine itself helps inhibit conventional NMDA receptors, perhaps this also represents an excitatory homeostasis mechanism with respect to just glycine?

I didn't see any part in the abstract where they tried to compare amounts of each receptor in specific areas of the brain. Or hell, they could still be concentrated in different parts of the brain, and just be involved in the same neural circuit.

What would also be interesting is to find the binding nature of the serine on the glycine receptor catalysis (i.e., noncompetitive or uncompetitive), as well as that of serine's inhibition at the NMDA receptor (science knows the latter quite well, but I'm too lazy to dig it up now).

My head hurts now. Need a 5HT1 antagonist ;) [Edited: I need a 5HT1 AGONIST like sumatriptan, hehe]

Edited by herrfous
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  • 6 years later...
  • 7 months later...

Has anyone tried glycine for schizophrenia, schizoaffective, or bipolar?


posting even though it's old.  i did heavy doses of glycine powder but couldn't injest enough to have a huge impact.  reading on the new medications they're working on targeting the glutamate receptors had gotten me thinking.  doc said best to wait for them to develop something instead of self-medicating.

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