β-Adrenoreceptor agonists and antagonists modulate the activity of α_2-adrenoreceptors in rat cortex cerebral membranes

摘要

The influence of isoprenaline- and propranolole-induced activation and inhibition of β-adrenoreceptors on the specific nonselective α_2-antagonist [~3H]RX821002 binding was studied on rat cerebral cortex subcellular membrane fractions. It was shown that the ligand-receptor interaction for α_2-adrenoreceptors corresponded to the model that assumed the presence of one receptor pool and binding of two ligand molecules to a receptor dimer. The following parameters were determined for [~3H]RX821002 binding to α_2-adrenoreceptors: K _(d1) = 1.57 ± 0.27 nM, B _(max) = 7.24 ± 1.63 fmol/mg of protein, n = 2. In the case of isoprenaline-induced activation of β-adrenoreceptors the binding of radiolabeled ligand to α_2-adrenoreceptors was described by the same model. The affinity of α_2-adrenoreceptors for [3H]RX821002 decreased more than twofold (K _d = 3.55 ± 0.02 nM) and the quantity of active receptors increased by 69% (B _(max) = 12.24 ± 0.06 fmol/mg of protein). Propranolole changed the model of ligand binding, and two pools of receptors were detected with the following parameters: K _(d1) = 0.61 ± 0.02 nM, K _(d2) = 3.41 ± 0.13 nM, B _(ml) = 1.88 ± 0.028 fmol/mg of protein, B _(m2) = 9.27 ± 0.08 fmol/mg of protein, n = 2. The data suggest that α_2-adrenoreceptors in subcellular membrane fractions from rat cerebral cortex exist in dimeric form. Isoprenaline and propranolole exhibit modulating effect on the specific antagonist binding to α_2- adrenoreceptors, which results in the inhibition and alteration of [ 3H]RX821002 binding parameters.