DIFFERENTIAL COUPLING OF D1 AND D5 DOPAMINE-RECEPTORS TO GUANINE-NUCLEOTIDE-BINDING PROTEINS IN TRANSFECTED GH(4)C(1) RAT SOMATOMAMMOTROPHIC CELLS

D1 and D5 dopamine receptor genes, stably expressed in GH(4)C(1) rat s omatomammotrophic cells, display identical binding values and stimulat e adenylate cyclase. Approximately 60% of D1 receptors were in the ago nist high-affinity state and were converted to the low-affinity slate by 100 mu M guanyl-5'-ylimidodiphosphate [Gpp(NH)p]. Of the 48% of D5 receptors in the high-affinity state, only half were modulated by 100 mu M Gpp(NH)p; in the presence of the G protein activator, AIF(4)(-), the high-affinity sites of D5 receptors were abolished by Gpp(NH)p, su ggesting tight coupling between D5 receptors and G proteins. The high- affinity sites of D1, but not D5, receptors were reduced after pertuss is toxin treatment of cells. Thus, whereas D1 receptors in GH(4)C(1) c ells couple to both G(s), the G stimulatory protein, and a pertussis t oxin-sensitive G protein, D5 receptors couple to G(s) and a pertussis toxin-insensitive G protein. Neither D1 nor D5 receptors were able to stimulate phosphoinositide metabolism in these cells. The ability of D 5, but not D1, receptors to couple to novel G proteins may be signific ant in assigning a functional role for these receptors.