Amphetamine sensitization/schizophrenia and D2 dimerization - help decipher study?

[Cotcha Yankinov]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2942879/ - "We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6%) and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons."

So as I understand it, a receptor dimer is essentially two receptors "stuck" together, but what I'm confused about is what are the consequences of these D2 dimers? Increased dopamine sensitivity? Or is it dependent on what specific receptor complex is formed?

One dimer I'm particularly curious about is an adenosine A2A/D2 dimer - (http://www.ncbi.nlm.nih.gov/pubmed/11872740/) - " Long term exposure to A(2A)R and D(2)R agonists in D(2)R-cotransfected SH-SY5Y cells resulted in coaggregation, cointernalization and codesensitization of A(2A)R and D(2)R. These results give a molecular basis for adenosine-dopamine antagonism at the membrane level and have implications for treatment of Parkinson's disease and schizophrenia, in which D(2)R are involved."

Does anybody have any idea what the consequences of an adenosine/dopamine dimer would be on sleep? I could be horribly wrong but I was thinking as adenosine builds up during the day you would get more and more dopamine activation via the dimer (assuming activation of the adenosine portion of the receptor can have an affect on the dopamine receptor's conformation?), so having an adenosine/dopamine dimer would result in increased dopamine when there is increased adenosine? Which would be very counter productive to sleep.

 

[serotonin2A]

Receptor oligomers often have different signaling properties (different G protein coupling), regulation, and distribution compared with the monomers. The consequences depend on the specific receptors and what cell expresses the oligomerized receptors.

 

[Cotcha Yankinov]

Am I to understand that (for example in an adenosine A2A / D2 oligomer) that If dopamine binds there it might change the receptor conformation of the adenosine receptor portion signal through the adenosine portion? Or are the receptor conformations somewhat separate?

 

[serotonin2A]

Forming dimers may or may not change the confirmation. It is impossible to know without further testing.

 

[PINKoPANaTHER]

I wanted to answer but s2A basically said what I had in mind. Unless they study the Dimers specifically for conformational changes with bound ligands, it can't really be estimated even. When proteins form dimers, trimers etc. each new subunit can change the receptor dynamics in a unique way.