NMDAr polyamine site, functions?

[Limpet_Chicken]

Something I've often wondered, but never managed to find an in-detail breakdown of the function and purpose of it, is what the polyamine allosteric binding site on NMDA receptors is for, and what it does.

Anybody able to clue me in as to what its purpose is?

 

[sekio]

Presumably (and somewhat naively) it's for sensing the levels of polyamines, but then again I'm not sure they occur as neurotransmitters to any significant degree... it could be that it's simply a serendipitous discovery and nature has no use for it (that we know of, yet). Given the complexity of protein-small molecule interactions, I wouldn't be surprised if there are allosteric/modulatory sites that lack any native ligand and are exclusively bound by xenobiotics.

 

[Limpet_Chicken]

Well as far as it being a binding site for polyamines...not to appear TOO sarcastic, but I HAD got so far as to work that out

And as for receptorswithout natural endogenous ligands, do you mean similar to the likes of say the aryl hydrocarbon nuclear receptor, for which no endogenous agonist, AFAIK, is known and appears to have evolved from politicia...ehhm...invertebrate, sorry, my bad there, developmental regulation genes, but in people, activation seems to be a really bad thing.

 

[Abject]

 

[Limpet_Chicken]

What the fuck have whippits to do with the NMDA polyamine site?

IIRC the natural endogenous ligands for the polyamine site are spermine and spermidine. N2O is just a typical NMDA antagonist, a channel blocker, active at the PCP site etc. rather than at the likes of glycine or polyamine allosteric sites.

 

[Abject]

What the fuck has glycine got to do with the polyamine site?
see how that looks?
Did you do any googling? I literally did fuck all and learnt four different effects of spermine.

 

[Limpet_Chicken]

I mean, what does nitrous have to do with the polyamine site? AFAIK polyamine site agonists (selective ones, of course) aren't dissociative.

And I was referring to the glycine allosteric site, in differentiating the allosteric sites from the PCP site/glutamate site, wikipedia does refer to N2O potentiating glycine receptors, however this should not be confused with the glycine allosteric site on NMDARs. There is also another glycine receptor all in its own right, an inhibitory receptor, that with GABA receptors, glycine receptors not associated with NMDARs are the main two neurotransmitters involved in CNS inhibitory neurotransmission, this is the strychnine-sensitive glycine receptor, whilst the glycine allosteric NMDAr site is strychnine-insensitive.