Differential desensitization and phosphorylation of three cloned and transfected α2-adrenergic receptor subtypes

Hitoshi Kurose, Robert J. Lefkowitz

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98 Citations (Scopus)


Genes encoding 3 distinct subtypes of human α2-adrenergic receptor are known and are found, respectively, on chromosome 10, 4, and 2 (α2-C10, α2-C4, and α2-C2 adrenergic receptors). All 3 receptors inhibit adenylyl cyclase via G(i) proteins. To study and compare their regulatory properties we assessed the ability of each to undergo agonist-promoted desensitization and phosphorylation. When Chinese hamster ovary cells stably expressing each of the three receptor genes were incubated with epinephrine for 20 min, a marked decrease in sensitivity to subsequent agonist-mediated inhibition of adenylyl cyclase was observed for the α2-C10 and α2-C2 receptors but not for the α2-C4 receptors. When similar incubations were performed with 32P(i)-labeled cells and the receptors were immunoprecipitated with specific antibodies, α2-C10 and α2-C2 receptors were found to undergo an ~3-fold increase in receptor phosphorylation after epinephrine exposure. When transfected into COS cells epinephrine also stimulated phosphorylation of α2-C10 and α2-C2 receptors while having only a slight effect on α2- C4 receptors. Cotransfection of the cells with the cDNA encoding the β- adrenergic receptor kinase further increased receptor phosphorylation for α2-C10 and α2-C2 receptors while having little or no effect on α2-C4 receptors. Moreover purified and reconstituted recombinant α2-C10 receptors could be phosphorylated in an agonist-dependent fashion whereas α2-C4 receptors could not. These observations suggest receptor subtype-specific differences in susceptibility to regulatory phosphorylation and desensitization.

Original languageEnglish
Pages (from-to)10093-10099
Number of pages7
JournalJournal of Biological Chemistry
Issue number13
Publication statusPublished - Apr 1 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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