咪唑啉的受体相互作用：通过咪唑啉激动剂的相对效价、亲和力和效能区分大鼠和兔主动脉的α-肾上腺素能受体
Receptor interactions of imidazolines: alpha-adrenoceptors of rat and rabbit aortae differentiated by relative potencies, affinities and efficacies of imidazoline agonists.
作者信息
Ruffolo R R, Waddell J E
出版信息
Br J Pharmacol. 1982 Sep;77(1):169-76. doi: 10.1111/j.1476-5381.1982.tb09283.x.
1 Noradrenaline and a series of imidazolines were used to characterized and differentiate the postsynaptic alpha-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 greater than noradrenaline greater than tramazoline greater than tetrahydrozoline greater than clonidine was obtained in rabbit aorta and an order of noradrenaline greater than clonidine greater than tramazoline greater than 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 greater than tramazoline greater than tetrahydrozoline greater than clonidine, whereas in rat aorta it was, clonidine greater than tetrahydrozoline greater then tramazoline greater than 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 alpha-adrenoceptors in these tissues are different. While the postsynaptic alpha-adrenoceptor of rabbit aorta is clearly of the alpha 1-subtype, the exact nature of the postsynaptic alpha-receptor of rat aorta is not clear. The unique alpha-receptor of rat aorta has properties of both alpha 1- and alpha 2-adrenoceptors.
用去甲肾上腺素和一系列咪唑啉来表征和区分大鼠和家兔主动脉的突触后α - 肾上腺素能受体。
每个组织中的剂量 - 反应曲线显示，这些化合物之间激动剂活性的特征存在显著差异。根据每种化合物的半数有效剂量（ED50）值，在家兔主动脉中得到的效价顺序为：羟甲唑啉＞去甲肾上腺素＞曲马唑啉＞四氢唑啉＞可乐定；在大鼠主动脉中得到的顺序为：去甲肾上腺素＞可乐定＞曲马唑啉＞羟甲唑啉。四氢唑啉在大鼠主动脉中无激动剂活性。
测定了大鼠和家兔主动脉中每种激动剂的解离常数。同样，观察到组织之间存在差异，以至于两种组织中咪唑啉的亲和力顺序完全相反。在家兔主动脉中顺序为：羟甲唑啉＞曲马唑啉＞四氢唑啉＞可乐定；而在大鼠主动脉中顺序为：可乐定＞四氢唑啉＞曲马唑啉＞羟甲唑啉。在可乐定和羟甲唑啉中观察到了极端的组织选择性，可乐定在大鼠主动脉中的亲和力约高125倍，羟甲唑啉在家兔主动脉中的亲和力约高4倍。
所研究的咪唑啉的相对效能绝对值及其顺序在两种组织之间也有所不同。羟甲唑啉和曲马唑啉在家兔主动脉中的相对效能比在大鼠主动脉中高15倍以上。此外，四氢唑啉在家兔主动脉中的相对效能比可乐定高，而在大鼠主动脉中情况相反。
去甲肾上腺素和一系列咪唑啉在大鼠和家兔主动脉中的效价、亲和力和相对效能顺序的差异表明，这些组织中的突触后α - 肾上腺素能受体是不同的。虽然家兔主动脉的突触后α - 肾上腺素能受体显然是α1亚型，但大鼠主动脉突触后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肾上腺素能受体的特性。
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