RECEPTOR INTERACTIONS OF IMIDAZOLINES: α‐ADRENOCEPTORS OF RAT AND RABBIT AORTAE DIFFERENTIATED BY RELATIVE POTENCIES, AFFINITIES AND EFFICACIES OF IMIDAZOLINE AGONISTS
RECEPTOR INTERACTIONS OF IMIDAZOLINES: α‐ADRENOCEPTORS OF RAT AND RABBIT AORTAE DIFFERENTIATED BY RELATIVE POTENCIES, AFFINITIES AND EFFICACIES OF IMIDAZOLINE AGONISTS
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咪唑啉受体相互作用：通过咪唑啉激动剂的相对效力、亲和力和功效来区分大鼠和兔主动脉的 α-肾上腺素受体
DOI：
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发表时间：
1982
影响因子：
7.3
通讯作者：
J. E. Waddell
中科院分区：
文献类型：
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作者：
R. Ruffolo;J. E. Waddell
1用去甲肾上腺素和一系列咪唑啉对大鼠和家兔海马突触后α-肾上腺素受体进行了表征和区分。2各组织中的剂量反应曲线显示化合物之间激动剂活性特征存在显著差异。根据各化合物的ED 50值，在兔主动脉中得到羟甲唑啉>去甲肾上腺素>曲马唑啉>四氢唑啉>可乐定的效力等级顺序，在大鼠主动脉中得到去甲肾上腺素>可乐定>曲马唑啉>羟甲唑啉的效力等级顺序。四氢唑啉对大鼠主动脉无激动活性。3测定了大鼠和兔睾丸中每种激动剂的解离常数。同样，观察到组织之间的差异，其程度为咪唑啉的亲和力的等级顺序对于两种组织完全相反。在兔主动脉中，羟甲唑啉>曲马唑啉>四氢唑啉>可乐定;在大鼠主动脉中，可乐定>四氢唑啉>曲马唑啉>羟甲唑啉。可乐定和羟甲唑啉的组织选择性极端，可乐定在大鼠主动脉中的亲和力高出约125倍，羟甲唑啉在兔主动脉中的亲和力高出约4倍。4所研究的咪唑啉类化合物的相对功效的绝对值及其等级顺序在两种组织之间也不同。羟甲唑啉和曲马唑啉在兔主动脉中的相对效力是在大鼠主动脉中的15倍以上。此外，四氢唑啉有更大的相对效力比可乐定在兔主动脉，而在大鼠主动脉则匡威。5去甲肾上腺素和一系列咪唑啉在大鼠和兔睾丸中的效力、亲和力和相对效力的等级顺序的差异表明，这些组织中的突触后α-肾上腺素受体是不同的。虽然兔主动脉的突触后α-肾上腺素受体显然是α1-亚型，但大鼠主动脉的突触后α-受体的确切性质尚不清楚。大鼠主动脉独特的α-受体具有α1-和α2-肾上腺素受体的特性。
1 Noradrenaline and a series of imidazolines were used to characterize and differentiate the postsynaptic α‐adrenoceptors of rat and rabbit aortae. 2 Dose‐response curves in each tissue revealed marked differences in the profile of agonist activity among the compounds. Based on the ED50 values for each compound, a rank order of potency of oxymetazoline > noradrenaline > tramazoline > tetrahydrozoline > clonidine was obtained in rabbit aorta and an order of noradrenaline > clonidine > tramazoline > oxymetazoline was obtained in rat aorta. Tetrahydrozoline had no agonist activity in rat aorta. 3 Dissociation constants were determined for each agonist in rat and rabbit aortae. Again, differences between the tissues were observed to the extent that the rank order of affinities for the imidazolines were exactly opposite for the two tissues. In rabbit aorta the order was, oxymetazoline > tramazoline > tetrahydrozoline > clonidine, whereas in rat aorta it was, clonidine > tetrahydrozoline > tramazoline > oxymetazoline. The extremes in tissue selectivity were observed with clonidine, which had approximately 125 fold higher affinity in rat aorta, and oxymetazoline, which had approximately 4 times higher affinity in rabbit aorta. 4 The absolute values of relative efficacies of the imidazolines studied, and their rank order, also differed between the two tissues. The relative efficacies of oxymetazoline and tramazoline were more than 15 fold greater in rabbit aorta than in rat aorta. Furthermore, tetrahydrozoline had a greater relative efficacy than clonidine in rabbit aorta while the converse was true in rat aorta. 5 Differences in the rank order of potency, affinity and relative efficacy of noradrenaline and a series of imidazolines in rat and rabbit aortae indicate that the postsynaptic α‐adrenoceptors in these tissues are different. While the postsynaptic α‐adrenoceptor of rabbit aorta is clearly of the α1‐subtype, the exact nature of the postsynaptic α‐receptor of rat aorta is not clear. The unique α‐receptor of rat aorta has properties of both α1‐ and α2‐adrenoceptors.