title: Classification of beta-adrenergic subtypes in immature rabbit bone marrow erythroblasts.
abstract: The beta-adrenergic receptors of immature rabbit bone marrow erythroid cells (proerythroblasts and basophilic erythroblasts) were identified. [125I]iodocyanopindolol bound to membrane preparations derived from these erythroblasts in a rapid, reversible and saturable manner. Scatchard analysis of binding data revealed a single class of binding sites (Hill coefficient of 0.954) with an apparent equilibrium dissociation constant (Kd) of 8 pM, and a density of binding sites (Bmax) of 1.53 pM/10(6) cells, corresponding to 920 receptors per cell. The binding of [125I]iodocyanopindolol was inhibited stereospecifically by concentrations of (-)-propranolol 2 orders of magnitude lower than by the (+)-isomer. Only L-isoprenaline and L-adrenaline activated the adenylate cyclase of immature rabbit erythroblasts, while L-noradrenaline, a beta 1-adrenergic agonist, was inactive. The order of potency of different agonists for displacement of bound [125I]iodocyanopindolol was: isoprenaline greater than adrenaline greater than noradrenaline with respective EC50 (concentration required for half maximal inhibition of binding) of 7.9 X 10(-7) M, 1.5 X 10(-5) M and 7.9 X 10(-5) M. This agonist potency series did not change with differentiation of rabbit bone marrow erythroblasts. The inhibition of specific [125I]iodocyanopindolol binding to immature cells by beta 1- and beta 2-selective drugs (noradrenaline, practolol, procaterol and butoxamine) resulted in linear Hofstee plots. The inhibition curves obtained with procaterol and butoxamine, with apparent Kd values of 3.1 X 10(-9) M and 4.9 X 10(-9) M, further evidence that the high-affinity binding sites correspond to a homogeneous beta 2-receptor subtype.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001853:Bone Marrow / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D004900:Erythroblasts / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004837:Epinephrine