Comparative characteristics of binding kinetics of specific antagonists by α1- and α2-adrenoceptors in rat cerebral cortex membranes

Abstract

The binding of specific nonselective α1- and α2-adrenoceptor antagonists [3H]prazosine and [3H]RX821002 has been studied on rat cerebral cortex synaptosomal membranes. It is shown that for α1-adrenoceptors the ligand-receptor interaction corresponds to the model assuming the presence of one pool of receptors and binding of two ligand molecules to the receptor. The parameters of [3H]prazosine binding to α1-adrenoceptors were: Kd= 1.56 ± 0.17 nM, Bmax = 30.25 ± 1.78 fmol/mg protein, n = 2. The parameters of [3H]RX821002 binding to α2-adrenoceptors were: Kd = 1.94 ± 0.08 nM, Bmax = 12.77 ± 3.17 fmol/mg protein, n = 2. For α2 -adrenoceptors the ligand-receptor interaction corresponded to the same model. For α1 - and α2-adrenoceptor antagonists the dissociation constants (Kd) are approximately equal (1.56 ± 0.17 and 1.94 ± 0.08 nM, respectively), but the concentration of α2-adrenoceptors is two times lower than that of α1-adrenoceptors ( 12.77 ± 3.17 and 30.25 ± 1.78 fmol/mg protein, respectively). The efficiency (E = Bmax/2Kd) of the ligand binding to α1-adrenoceptors is 2.3 times higher than that to α2-adrenoceptors (7.46 ± 1.32 and 3.29 ± 0.68 fmol/mg protein/nM, respectively. The data suggest that α1- and α2 -adrenoceptors in rat cerebral cortex exist as dimers.