title: N-Bromoacetyl-amino-cyanopindolol: a highly potent beta-adrenergic affinity label blocks irreversibly a non-protein component tightly associated with the receptor.
abstract: A new chemical affinity label for the beta-adrenergic receptor, based on the structure of pindolol, has been synthesized and iodinated with 125I. The compound, N-bromoacetylamino-cyanopindolol (BAM-CYP), has an apparent dissociation constant of 44 +/- 7 pM towards the turkey erythrocyte membranes. This compound blocks irreversibly both the ability of beta-adrenergic receptors to bind 125I-cyanopindolol and the ability of beta-receptors to activate adenylate cyclase in the presence of beta-agonists. Furthermore, the irreversible binding of BAM-CYP to half of the beta-receptor sites abolishes the ligand binding activity of all the sites. These findings suggest that the beta-receptor is oligomeric in its native state. Although 125I-BAM-CYP blocks irreversibly and specifically the beta-adrenergic receptor, it does so by labeling a non-protein component, most probably a water-soluble lipid. The labeling is stereospecific since it is prevented by l-propranolol and not by d-propranolol. It is suggested that this lipid is tightly associated with the receptor in close proximity to the binding site. It is also suggested that this water-soluble lipid fraction may prove crucial for the optimal interaction between the beta-adrenergic receptor and the components of adenylate cyclase.
authors.forename: M
authors.initials: M
authors.lastname: Chorev
authors.forename: A
authors.initials: A
authors.lastname: Feigenbaum
authors.forename: A K
authors.initials: AK
authors.lastname: Keenan
authors.forename: C
authors.initials: C
authors.lastname: Gilon
authors.forename: A
authors.initials: A
authors.lastname: Levitzki
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000345:Affinity Labels / Q000138:chemical synthesis*; D000818:Animals; D001667:Binding, Competitive; D004082:Dihydroalprenolol / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D010869:Pindolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014422:Turkeys
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000345:Affinity Labels; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D020120:Iodocyanopindolol; C044136:N-(bromoacetylamino)cyanopindolol; D010869:Pindolol