Calcium- and potassium-channel blockers interact with alpha-adrenoceptors.

The so-called calcium antagonist D-600 and agents that enhance the influx of calcium ions into nerve terminals during action potentials (4-aminopyridine, tetraethylammonium, guanidine) interact with alpha-adrenoceptors. The interaction was revealed by binding experiments in vitro with the alpha 2- and alpha 1-specific ligands [3H]clonidine and [3H]prazosin, resp. D-600 binds in a competitive manner to alpha 2- and alpha 1-adrenoceptors in rat-brain membranes. [3H]Prazosin was used to identify alpha 1-adrenoceptors in rat-heart-membrane fragments. D-600 inhibited the binding of the tritiated antagonist, in a manner similar to that seen in rat-brain membranes. 4-Aminopyridine, guanidine and tetraethylammonium blocked no-competitvely the binding of [3H]clonidine in brain membranes. There ws little or no effect of these agents on the binding of [3H]prazosin to alpha 1-adrenoceptors in rat heart or brain. The results indicate that D-600 binds to a region common to alpha 1- and alpha 2-adrenoceptors, whereas the potassium-channel blockers reveal a structural feature of the alpha 2-adrenoceptors in brain membranes which is also present in voltage-dependent potassium channels but is not shared by alpha 1-adrenoceptors.