DIFFERENTIAL-EFFECTS OF THE CALCIUM ENTRY BLOCKER D-600 ON CONTRACTIONS OF RAT AND GUINEA-PIG AORTAS, ELICITED BY VARIOUS ALPHA-1 ADRENOCEPTOR AGONISTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (2) , 515-521
Abstract
Contractions of rat and guinea pig aortas to the .alpha.-adrenoceptor agonists l-norepinephrine, cirazoline, ST 587 [2-(2-chloro-5-trifluoromethylphenylimino) imidazoline], clonidine and Sgd 101/75 [4-(2-imidazolinamino)-2-methylindazole hydrochloride], and the effect of Ca2+ entry blockade by D-600 on the responses evaluated. In rat aorta, D-600 (10-8-10-5 M) effectively and concentration-dependently reduced the maximal responses to St 587, clonidine and Sgd 101/75 (maximal percentage inhibition 84 .+-. 2.1, 86 .+-. 4.1 and 65 .+-. 2.8, n = 5-6, respectively) in contrast to those of l-norepinephrine and cirazoline (maximal percentage inhibition 23 .+-. 2.1 and 21 .+-. 4.1, n = 6, respectively). Reducing the receptor number on rat aorta by approximately 85% by means of the irreversible blocker dibenamine did not result in a greater sensitivity of norepinephrine-induced contractions toward D-600. Prazosin was found 800-1000 times more potent than yohimbine in antagonizing the contractile effects of St 587, clonidine and cirazoline on rat and guinea pig aortas. No difference existed between the pA2 [competitive antagonistic activity] values of prazosin and yohimbine against the different agonists; the pA2 values of prazosin and yohimbine were significantly higher in rat aorta than those in guinea pig aorta. The results can be explained by assuming the existence of 2 different agonist recognition sites on the .alpha.-1 adrenoceptor on rat aorta, whereas the .alpha.-1 adrenoceptor on guinea pig aorta contains 1 agonist recognition site only. The architecture of the .alpha.-1 adrenoceptor on rat aorta must therefore be different from that in guinea pig aorta.