Eskinder H, Gross G J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Pharmacology. 1987;35(5):272-8. doi: 10.1159/000138320.
The purpose of the present study was to determine if the calcium channel activator, Bay K 8644, enhances the vasoconstrictor actions of selective alpha 1- and alpha 2-adrenoceptor agonists in canine saphenous vein. Phenylephrine (PE) and St 587 were used as fully and partially selective alpha 1-adrenoceptor agonists, B-HT 920 and B-HT 958 were used as fully and partially selective alpha 2-adrenoceptor agonists. Bay K 8644 (10(-8) M) markedly potentiated B-HT-958-mediated vasoconstrictor responses with a leftward shift and an increase in the maximum response of the logarithmic dose-response curve. Bay K 8644 produced less potentiation of responses to B-HT 920 and had minimal effects on responses to St 587 and PE. The intrinsic activities of the alpha-adrenoceptor agonists, as compared to the maximum response obtained by norepinephrine, in decreasing order, were PE greater than St 587 greater than B-HT 920 greater than B-HT 958, whereas the susceptibility of alpha-adrenoceptor agonists to potentiation by Bay K 8644 in decreasing order were B-HT 958 greater than B-HT 920 greater than St 587 greater than PE. These results suggest that Bay K 8644 preferentially improves the receptor-response coupling of alpha-adrenoceptor agonists with low intrinsic activity (alpha 2-agonists) versus agonists with high intrinsic activity (alpha-agonists) in canine saphenous vein.
本研究的目的是确定钙通道激活剂Bay K 8644是否能增强犬隐静脉中选择性α1和α2肾上腺素能受体激动剂的血管收缩作用。苯肾上腺素（PE）和St 587分别用作完全和部分选择性α1肾上腺素能受体激动剂，B-HT 920和B-HT 958分别用作完全和部分选择性α2肾上腺素能受体激动剂。Bay K 8644（10^(-8) M）显著增强了B-HT-958介导的血管收缩反应，使对数剂量反应曲线向左移位并增加最大反应。Bay K 8644对B-HT 920反应的增强作用较小，对St 587和PE反应的影响最小。与去甲肾上腺素获得的最大反应相比，α肾上腺素能受体激动剂的内在活性由高到低依次为PE＞St 587＞B-HT 920＞B-HT 958，而α肾上腺素能受体激动剂对Bay K 8644增强作用的敏感性由高到低依次为B-HT 958＞B-HT 920＞St 587＞PE。这些结果表明，在犬隐静脉中，Bay K 8644优先改善低内在活性的α肾上腺素能受体激动剂（α2激动剂）与高内在活性的激动剂（α激动剂）的受体-反应偶联。
