BINDING OF [H-3] PRAZOSIN TO PORCINE AORTIC MEMBRANES - INTERACTION OF CALCIUM-ANTAGONISTS WITH VASCULAR ALPHA-1 ADRENOCEPTORS

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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 .mu.M), D600 (Ki = 0.86 .mu.M), nicardipine (Ki = 2.3 .mu.M) and d-cis dilitiazem (Ki = 9.8 .mu.M). Nifedipine and nitrendipine, potent dihydropyridine Ca antagonists, only partially inhibited the [3H]prazosin binding, up to 10-4 M. I-Cis and dl-trans dilitiazem, the less potent steroisomers 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 dilitiazem 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.