Pharmacological analysis of a dopamine D2Short:Gαofusion protein expressed in Sf9 cells

Abstract
A dopamine D2Short receptor:Gαo fusion protein was expressed in Sf9 cells using the baculovirus expression system. [3H]Spiperone bound to D2Short:Gαo with a pKd≈10. Dopamine stimulated the binding of [35S]guanosine-5′-O-(3-thio)triphosphate (GTPγS) to D2Short:Gαo expressed with Gβ1γ2 (Emax>460%; pEC50 5.43±0.06). Most of the putative D2 antagonists behaved as inverse agonists (suppressing basal [35S]GTPγS binding) at D2Short:Gαo/Gβ1γ2 although (−)-sulpiride and ziprasidone were neutral antagonists. Competition of [3H]spiperone binding by dopamine and 10,11-dihydroxy-N-n-propylnorapomorphine revealed two binding sites of different affinities, even in the presence of GTP (100 μM). The D2Short:Gαo fusion protein is therefore a good model for characterising D2 receptors

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