Muscarinic cholinoceptor agonists and antagonists are modulators of the activity of α1-adrenoceptors in the membranes of rat cerebral cortex

Abstract

The effects of activation and inhibition of muscarinic cholinoceptors by carbachol and atropine on the binding of specific nonselective α1-antagonist [3H]prazosine in synaptosomal membranes of rat cerebral cortex have been studied. It has been shown that the ligand-receptor interaction of α1-adrenoceptors corresponds to the model suggesting the presence of a single receptor pool and the binding of two ligand molecules to the receptor. The parameters of [3H]prazosine binding to α1-adrenoceptors were as follows: Kd = 1.56 ± 0.17 nM, Bmax = 30.25 ± 1.78 fmol/mg protein, n = 2. Upon inhibition of muscarinic cholinoceptors by atropine or their activation by carbachol, the radiolabelled ligand is bound to α1-adrenoceptors according to the same model but at n = 1. In the presence of atropine, the sensitivity of α1-adrenoceptors to [3H]prazosine decreases more than twofold (Kd = 3.52 ± 0.36 nM) and the concentration of the active receptors is 36% lower (Bmax = 19.45 ± 1.46 fmol/mg protein). Carbachol does not reduce the affinity of adrenoceptors to the ligand, while the concentration of active receptors decreases like in the case of atropine. It is supposed that α1-adrenoceptors in the membranes of rat cerebral cortex exist as dimers. The modulating effects of atropine and carbachol on the binding of specific antagonist by α1-adrenoceptors are exhibited as changes in the general character of binding (monomerization of α1-adrenoceptors) and as inhibitory effect on the [3H]prazosine binding parameters.