Identification of a novel M_r = 76-kDa form of beta-adrenergic receptors

The structure of the human β-adrenergic receptor in purified basal membranes of human placental syncytiotrophoblast was probed using photoaffinity labeling. Basal membranes display a high specific activity of receptors (4-5 pmol/mg protein) and possess both β₁- and β₂-adrenergic receptors subtypes. Autoradioraphy of membranes that were incubated with the β-adrenergic antagonist [¹²⁵I]iodoazidobenzylpindolol, photolyzed and then subjected to sodium dodecylsulfate-polyacrylamide gel electrophoresis, identified four radiolabeled peptides. M_r = 65-kDa, 54-kDa, 43-kDa and a novel higher molecular weight 76-kDa form of the receptor. Photoaffinity labeling of each of these four peptides displayed the pharmacological properties expected for true β-adrenergic receptors. The 76-kDa photoaffinity labeled receptor peptide observed in human placenta basal membranes has not been reported elsewhere. Competition studies with the β₁-selective ligand CGP-20712A demonstrate that the photoaffinity labeled receptor peptides are composed of both β₁- and β₂-adrenergic receptor subtypes.