Abstract
Contractions of rat and guinea-pig aortas to the alpha-adrenoceptor agonists I-norepinephrine, cirazoline , St 587, clonidine and Sgd 101/75 and the effect of calcium entry blockade by D 600 on the responses were evaluated. In rat aorta, D-600 (10(-8) to 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 I-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 to 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 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 two different agonist recognition sites on the alpha-1 adrenoceptor on rat aorta, whereas the alpha-1 adrenoceptor on guinea-pig aorta contains one agonist recognition site only. The architecture of the alpha-1 adrenoceptor on rat aorta must therefore be different from that in guinea-pig aorta.
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