Differential coupling of D1 and D5 dopamine receptors to guanine nucleotide binding proteins in transfected GH4C1 rat somatomammotrophic cells.
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.
Kimura
K
K
Department of Pediatrics, Georgetown University Medical Center, Washington D.C. 20007, USA.
Sela
S
S
Bouvier
C
C
Grandy
D K
DK
Sidhu
A
A
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
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