Beckeringh J J, Thoolen M J, de Jonge A, Wilffert B, Timmermans P B, van Zwieten P A
J Pharmacol Exp Ther. 1984 May;229(2):515-21.
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.
评估了大鼠和豚鼠主动脉对α-肾上腺素能受体激动剂去甲肾上腺素、西拉唑啉、St 587、可乐定和Sgd 101/75的收缩反应，以及D 600对钙内流的阻断作用对这些反应的影响。在大鼠主动脉中，D-600（10^(-8)至10^(-5) M）有效且呈浓度依赖性地降低了对St 587、可乐定和Sgd 101/75的最大反应（最大抑制百分比分别为84±2.1、86±4.1和65±2.8，n = 5 - 6），与之形成对比的是去甲肾上腺素和西拉唑啉（最大抑制百分比分别为23±2.1和21±4.1，n = 6）。通过不可逆阻断剂双苄胺使大鼠主动脉上的受体数量减少约85%，并未导致去甲肾上腺素诱导的收缩对D 600更敏感。发现哌唑嗪在拮抗St 587、可乐定和西拉唑啉对大鼠和豚鼠主动脉的收缩作用方面比育亨宾强800至1000倍。哌唑嗪和育亨宾对不同激动剂的pA2值之间没有差异；哌唑嗪和育亨宾在大鼠主动脉中的pA2值显著高于豚鼠主动脉中的pA2值。这些结果可以通过假设大鼠主动脉上的α-1肾上腺素能受体存在两个不同的激动剂识别位点来解释，而豚鼠主动脉上的α-1肾上腺素能受体仅包含一个激动剂识别位点。因此，大鼠主动脉上α-1肾上腺素能受体的结构必定与豚鼠主动脉上的不同。
