In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 18, No. 21 ( 1998-11-01), p. 8692-8699
Abstract:
D 2L dopamine receptor activation results in rapid inhibition and delayed heterologous sensitization of adenylate cyclase in several host cell types. The D 2L dopamine receptor was stably transfected into NS20Y neuroblastoma cells to examine inhibition and sensitization in a neuronal cell environment and to identify the particular G-proteins involved. Acute activation of D 2L receptors with the selective D 2 agonist quinpirole inhibited forskolin-stimulated cAMP accumulation, whereas prolonged incubation (2 hr) with quinpirole resulted in heterologous sensitization (more than twofold) of forskolin-stimulated cAMP accumulation in NS20Y-D 2L cells. To unambiguously identify the pertussis toxin (PTX)-sensitive G-proteins responsible for inhibition and sensitization, we used viral-mediated gene delivery to assess the ability of genetically engineered PTX-resistant G-proteins (Gα i1 *, Gα i2 *, Gα i3 *, and Gα o *) to rescue both responses after PTX treatment. The expression and function of individual recombinant G-proteins was confirmed with Western blotting and inhibition of GTPγS-stimulated adenylate cyclase, respectively. To assess the specificity of D 2L -Gα coupling, cells were infected with herpes simplex virus (HSV) recombinants expressing individual PTX-resistant G-protein α subunits and treated with PTX, and quinpirole-induced responses were measured. Infection of NS20Y-D 2L cells with HSV-Gα o * rescued both inhibition and sensitization in PTX-treated cells, whereas infection with HSV-Gα i1 *, HSV-Gα i2 *, or HSV-Gα i3 * failed to rescue either response. In summary, the current study provides strong evidence that the D 2L dopamine receptor couples to Gα o in neuronal cells, and that this coupling is responsible for both the acute and subacute effects of D 2 receptor activation on adenylate cyclase activity.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.18-21-08692.1998
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
1998
detail.hit.zdb_id:
1475274-8
SSG:
12
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