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.
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003000:Clonidine / Q000378:metabolism; D005711:Gallopamil / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives*
D000631:Aminopyridines; D006146:Guanidines; D007473:Ion Channels; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013757:Tetraethylammonium Compounds; D005711:Gallopamil; D014700:Verapamil; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D011224:Prazosin