Multiple Coupling of Human D5 Dopamine Receptors to Guanine Nucleotide Binding Proteins GS and Gz |
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Authors: | Anita Sidhu Kazuhiro Kimura Misook Uh Beatrix H. White Shutish Patel |
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Affiliation: | Department of Pediatrics, Georgetown University Medical Center, Washington, D.C.;and; Neurobiology Research Laboratory, VA Connecticut Healthcare System, Newington, Connecticut, U.S.A. |
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Abstract: | Abstract: We have demonstrated previously that D1 dopamine receptors are coupled to both Gsα and Goα. We examine here the coupling between human D5 dopamine receptors and G proteins in transfected rat pituitary GH4C1 cells. Similar to D1 receptors, cholera toxin treatment of cells reduced, but did not abolish, D5 agonist high-affinity binding sites, indicating D5 receptors couple to both Gsα and cholera toxin-insensitive G proteins. The interaction between D5 receptors and Gsα was confirmed by immunoprecipitation studies and by the ability of D5 receptors to stimulate adenylyl cyclase. Unlike D1 receptors, D5 receptors did not display any pertussis toxin-sensitive G-protein coupling to Goα or Giα. D5 receptors were also not coupled to Gqα and were unable to mediate phosphatidylinositol metabolism. Instead, D5 sites appeared to be coupled to an AIF−4-sensitive, N -ethylmaleimide-resistant G protein. Anti-Gzα caused immunoprecipitation of 24.2 ± 5.2% of G protein-associated D5 receptors, indicating coupling between D5 and Gzα. The coupling to Gzα was specific for D5 receptors, because similar associations were not detected between D1 receptors and Gzα. |
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Keywords: | Dopamine receptors G proteins Signal transduction Cholera toxin Pertussis toxin |
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