Allosteric effects of atropine and carbachol on the activity of α2-adrenoceptors in rat brain cortex membranes

Abstract

Activation and inhibition of muscarinic cholinoceptors by atropine and carbachol are shown to exert allosteric effects on the binding of specific nonselective α2-adrenoceptor antagonist [3H]RX821002 in rat brain cortex membranes. The ligand-receptor interaction for α2-adrenoceptors corresponded to the model suggesting the presence of one homogeneous pool of receptors with two specific binding sites. The parameters of the [3H]RX821002 binding were as follows: [3H]RX821002 -Kd = 1.94 ± 0.08 nM, Bmax = 13.4 ± 1.8 fmol/mg protein, n = 2. The inhibition of muscarinic cholinoceptors by atropine induced an increase of affinity (Kd = 1.36 ± 0.12 nM) and a decrease of the α2-adrenoceptor density (Bmax = 10.18 ± 0.48 fmol/mg protein). The muscarinic cholinoceptor agonist carbachol induced an increase of the affinity (Kd = 1.56 ± 0.05 nM) and quantity of binding sites (Bmax = 16.61 ± 0.29 fmol/mg protein). As a result, under the influence of atropine and carbachol, the efficiency of binding (E = Bmax/2Kd) increased from 3.50 ± 0.40 to 5.60 ± 0.79 and 6.86 ± 0.20 fmol/mg protein/nM, respectively. The data suggest that α2-adrenoceptors exist in rat brain cortex as homodimers.