Takayanagi I, Koike K, Kawano K, Onozuka S
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Arch Int Pharmacodyn Ther. 1988 Jul-Aug;294:175-84.
Noradrenaline sensitivity (pD2-value) and agonist dissociation constant (pKA-value) were determined in the following 4 canine arteries: thoracic and abdominal aorta, mesenteric and renal. The experiments were done in the presence of beta- and alpha 2-adrenoceptor blockers, and inhibitors of neuronal and non-neuronal uptake of catecholamine. A positive correlation was found in the pD2- and pKA-values for noradrenaline (r = 0.976, P less than 0.05). The slope (0.92) was not significantly different from 1. The pD2- and pKp (negative log of dissociation constant of partial agonist)-values of clonidine, an alpha 1-adrenergic partial agonist, were also determined. There was a positive correlation between the pD2- and pKp-values (r = 0.974, P less than 0.05). Again, the slope (1.39) was not significantly different from 1. These results indicate that the regional difference in the pD2-values for noradrenaline and clonidine in canine arteries is due to the affinities to alpha 1-adrenoceptors and that there is a qualitative difference between alpha 1-adrenoceptor mechanisms in the arteries and veins. However, no positive correlation between the pD2-values for noradrenaline and clonidine was observed (r = 0.182, P greater than 0.05). Thus, it may be suggested that either the recognition sites for noradrenaline, clonidine and prazosin are different or else their mode of attachment to the same recognition site is not identical.
在以下4种犬类动脉中测定去甲肾上腺素敏感性(pD2值)和激动剂解离常数(pKA值):胸主动脉、腹主动脉、肠系膜动脉和肾动脉。实验在β和α2肾上腺素能受体阻滞剂以及儿茶酚胺神经元和非神经元摄取抑制剂存在的情况下进行。发现去甲肾上腺素的pD2值和pKA值之间呈正相关(r = 0.976,P < 0.05)。斜率(0.92)与1无显著差异。还测定了α1肾上腺素能部分激动剂可乐定的pD2值和pKp(部分激动剂解离常数的负对数)值。pD2值和pKp值之间呈正相关(r = 0.974,P < 0.05)。同样,斜率(1.39)与1无显著差异。这些结果表明,犬类动脉中去甲肾上腺素和可乐定pD2值的区域差异是由于对α1肾上腺素能受体的亲和力,并且动脉和静脉中的α1肾上腺素能受体机制存在质的差异。然而,未观察到去甲肾上腺素和可乐定的pD2值之间呈正相关(r = 0.182,P > 0.05)。因此,可能提示去甲肾上腺素、可乐定和哌唑嗪的识别位点不同,或者它们与同一识别位点的结合方式不同。