title: Binding of [3H]prazosin to porcine aortic membranes: interaction of calcium antagonists with vascular alpha-1 adrenoceptors.
abstract: The characteristics of [3H]prazosin binding and the interaction of Ca antagonists with alpha-1 adrenoceptors in the porcine aortic membranes were investigated. The binding characteristics of [3H]prazosin, namely, the kinetics and affinity of binding, saturability, competition by adrenergic agonists and antagonists, stereoselectivity and the localization of binding sites, indicated that [3H]prazosin binds specifically to the alpha-1 adrenoceptors in the sarcolemma of porcine aortic smooth muscle cells. In the inhibition study by several Ca antagonists, the specific binding of [3H]prazosin to aortic membranes was inhibited by verapamil (Ki = 0.66 microM), D600 (Ki = 0.86 microM), nicardipine (Ki = 2.3 microM) and d-cis diltiazem (Ki = 9.8 microM). Nifedipine and nitrendipine, potent dihydropyridine Ca antagonists, only partially inhibited the [3H]prazosin binding, up to 10(-4) M. l-Cis and dl-trans diltiazem, the less potent stereoisomers as Ca channel blockers compared with the d-cis form, showed a similar and greater potency as a competitor to alpha-1 adrenoceptors, respectively. These observations indicate that verapamil, D600, nicardipine and diltiazem interact with vascular alpha-1 adrenoceptors and that the potency of these compounds as a competitor to alpha-1 adrenoceptors does not parallel their potency as Ca channel blockers.
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013552:Swine; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D002118:Calcium; D011224:Prazosin