title: Differential coupling of D1 and D5 dopamine receptors to guanine nucleotide binding proteins in transfected GH4C1 rat somatomammotrophic cells.
abstract: D1 and D5 dopamine receptor genes, stably expressed in GH4C1 rat somatomammotrophic cells, display identical binding values and stimulate adenylate cyclase. Approximately 60% of D1 receptors were in the agonist high-affinity state and were converted to the low-affinity state by 100 microM guanyl-5'-ylimidodiphosphate [Gpp(NH)p]. Of the 48% of D5 receptors in the high-affinity state, only half were modulated by 100 microM Gpp(NH)p; in the presence of the G protein activator, AIF4-, the high-affinity sites of D5 receptors were abolished by Gpp(NH)p, suggesting tight coupling between D5 receptors and G proteins. The high-affinity sites of D1, but not D5, receptors were reduced after pertussis toxin treatment of cells. Thus, whereas D1 receptors in GH4C1 cells couple to both Gs, the G stimulatory protein, and a pertussis toxin-sensitive G protein, D5 receptors couple to Gs and a pertussis toxin-insensitive G protein. Neither D1 nor D5 receptors were able to stimulate phosphoinositide metabolism in these cells. The ability of D5, but not D1, receptors to couple to novel G proteins may be significant in assigning a functional role for these receptors.
authors.affiliation: Department of Pediatrics, Georgetown University Medical Center, Washington D.C. 20007, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Sela
authors.forename: C
authors.initials: C
authors.lastname: Bouvier
authors.forename: D K
authors.initials: DK
authors.lastname: Grandy
authors.forename: A
authors.initials: A
authors.lastname: Sidhu
mesh_terms: D037361:Adenylate Cyclase Toxin; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000031:analogs & derivatives / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D037361:Adenylate Cyclase Toxin; D017607:Aluminum Compounds; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D010566:Virulence Factors, Bordetella; D006165:Guanylyl Imidodiphosphate; D013006:Growth Hormone; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride