β-Adrenoreceptor agonists and antagonists modulate the activity of α2-adrenoreceptors in rat cortex cerebral membranes

Abstract

The influence of isoprenaline- and propranolole-induced activation and inhibition of β-adrenoreceptors on the specific nonselective α2-antagonist [3H]RX821002 binding was studied on rat cerebral cortex subcellular membrane fractions. It was shown that the ligand-receptor interaction for α2-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 α2-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 α2-adrenoreceptors was described by the same model. The affinity of α2-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 α2-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 α2-adrenoreceptors, which results in the inhibition and alteration of [3H]RX821002 binding parameters.