Selective Activation of Gao by D2L Dopamine Receptors in NS20Y

D2L dopamine receptor activation results in rapid inhibition and delayed heterologous sensitization of adenylate cyclase in sev-eral host cell types. The D2L dopamine receptor was stably transfected into NS20Y neuroblastoma cells to examine inhibi-tion and sensitization in a neuronal cell environment and to identify the particular G-proteins involved. Acute activation of D2L receptors with the selective D2 agonist quinpirole inhibited forskolin-stimulated cAMP accumulation, whereas prolonged incubation (2 hr) with quinpirole resulted in heterologous sen-sitization (more than twofold) of forskolin-stimulated cAMP ac-cumulation in NS20Y-D2L cells. To unambiguously identify the pertussis toxin (PTX)-sensitive G-proteins responsible for inhi-bition and sensitization, we used viral-mediated gene delivery to assess the ability of genetically engineered PTX-resistant G-proteins (Gai1*, Gai2*, Gai3*, and Gao*) to rescue both re