Schümann H J, Endoh M
Eur J Pharmacol. 1976 Apr;36(2):413-21. doi: 10.1016/0014-2999(76)90095-9.
Tha alpha-sympathomimetic agonists, clonidine, naphazoline, methoxamine, oxymetazoline and phenylephrine were used to further characterize the alpha-adrenoceptors mediating the positive inotropic effect in the isolated papillary muscle of the rabbit heart. The maximal inotropic effects of these amines were compared with the effect of isoprenaline and it was examined whether or not these amines compete for alpha-adrenoceptors. On the papillary muscle stimulated at 0.5 Hz, phenylephrine showed a high affinity (pD2 value=6.13) and produced the most pronounced intrinsic activity of the alpha-sympathomimetic amines. Therefore, the intrinsic activity of phenylephrine, in the presence of prindolol (3 X 10(-8) M), was used for comparison with those of the other alpha-agonists. Clonidine caused a positive inotropic effect: the intrinsic activity amounted to 0.32 of that of phenylephrine; the affinity was the highest among the amines tested (pD2 value=6.46); its effect was inhibited by 10(-6) M phentolamine. The affinity and the intrinsic activity of naphazoline were slightly lower than those of clonidine. Methoxamine showed a relatively high intrinsic activity (0.56) but the lowest affinity (4.68). Oxymetazoline did not cause any positive inotropic effect. Clonidine, naphazoline and oxymetazoline antagonized the positive inotropic effect of phenylephrine, mediated via the alpha-adrenocaptors in the presence of 3 X 10(-8) M prindolol, in a competitive manner. This observation suggests that these alpha-sympathomimetic amines compete with phenylephrine for the same receptor site. Thus the present results provide additional evidence for alpha-adrenoceptors mediating the positive inotropic actions of sympathomimetic amines in the rabbit papillary muscle.
使用α-拟交感神经激动剂可乐定、萘甲唑啉、甲氧明、羟甲唑啉和去氧肾上腺素，进一步研究介导兔心脏离体乳头肌正性肌力作用的α-肾上腺素能受体。将这些胺类药物的最大正性肌力作用与异丙肾上腺素的作用进行比较，并检测这些胺类药物是否竞争α-肾上腺素能受体。在0.5Hz频率刺激的乳头肌上，去氧肾上腺素表现出高亲和力（pD2值=6.13），并且产生了α-拟交感神经胺类中最显著的内在活性。因此，在吲哚洛尔（3×10⁻⁸M）存在的情况下，使用去氧肾上腺素的内在活性与其他α-激动剂的内在活性进行比较。可乐定产生正性肌力作用：内在活性相当于去氧肾上腺素的0.32；在所测试的胺类中亲和力最高（pD2值=6.46）；其作用被10⁻⁶M酚妥拉明抑制。萘甲唑啉的亲和力和内在活性略低于可乐定。甲氧明表现出相对较高的内在活性（0.56），但亲和力最低（4.68）。羟甲唑啉未产生任何正性肌力作用。在3×10⁻⁸M吲哚洛尔存在的情况下，可乐定、萘甲唑啉和羟甲唑啉以竞争性方式拮抗由α-肾上腺素能受体介导的去氧肾上腺素的正性肌力作用。该观察结果表明，这些α-拟交感神经胺类与去氧肾上腺素竞争相同的受体位点。因此，本研究结果为α-肾上腺素能受体介导拟交感神经胺类在兔乳头肌中的正性肌力作用提供了额外证据。
