Neuroscience 2003 Abstract
| Presentation Number: | 469.14 |
|---|---|
| Abstract Title: | Investigation of D<sub>3</sub> dopamine receptor - AMPA receptor interactions in HEK293T cells. |
| Authors: |
Kim, O.*1
; Lovinger, D. M.2
; Kim, E.1
; Sibley, D. R.1
1Mol. NeuroPharmacol. Section, NINDS/NIH, Bethesda, MD 2MD, Building 10, Room 5C110 10 Ctr. Dr., MSC-1406, 20892-1406, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein linked Receptors -- Catecholamine receptors |
| Session: |
469. Dopamine Receptors III Poster |
| Presentation Time: | Monday, November 10, 2003 2:00 PM-3:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # D11 |
| Keywords: | DOPAMINE, DOPAMINE RECEPTOR, AMPA RECEPTOR, GLUTAMATE RECEPTOR |
We have previously shown (SFN 2002 Abstract #542.6) that D3 dopamine receptors (D3DARs) and AMPA receptor subunits can be co-immunoprecipitated from HEK293T cells. These effects were specific and suggested that D3 and AMPA receptors may form hetero-oligomers when expressed in the same cell. We have now investigated the functional consequences of these receptor-receptor interactions using intact cells. Using radioligand binding assays, we found that co-expression of the GluR2 or GluR3 subunits resulted in a 25-50% decrement in D3DAR expression levels. To examine D3DAR function, it was necessary to co-transfect adenylyl cyclase type V in the cells and then examine D3DAR-mediated inhibition of forskolin-stimulated cAMP accumulation. Both dopamine and quinpirole inhibited the adenylyl cyclase activity in a dose-dependent fashion. Co-expression of GluR2 with the D3DAR resulted in a 4-6 fold rightward shift in the agonist dose-response curves (increase in EC50) without a major effect on the maximum response. Interestingly, the addition of 30 μM AMPA to the cAMP assay abolished the shift in agonist potency such that the GluR2 subunit expression was without effect. These results suggest that D3DAR and GluR subunits may constitutively hetero-oligomerize in HEK293T cells and that this attenuates D3DAR-G protein coupling. Further, the state of D3DAR/GluR hetero-oligomerization may be dependent on agonist occupancy/activation of the GluR receptor. In terms of AMPA receptor function, co-expression of D3DARs with GluR1+2 in HEK293T cells did not alter the functional expression of GluR-mediated responses as measured by the density of current activated by 100 μM AMPA + 100 μM cyclothiazide. The expression of GluR2 also did not appear to be altered, as current/voltage relationships were linear. We are currently further investigating the effects of D3DAR expression on GluR activity.
Supported by NIH
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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