Hattori Y, Kanno M
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Eur J Pharmacol. 1997 Jun 25;329(2-3):165-8. doi: 10.1016/s0014-2999(97)00169-6.
We studied the alpha1-adrenoceptor subtypes mediating the positive inotropic effects of phenylephrine and noradrenaline as well as endogenous noradrenaline released by tyramine in rabbit papillary muscle. In the presence of propranolol, both phenylephrine and tyramine produced a positive inotropic effect in a concentration-dependent manner. WB4101 (N-[2-(2,6-dimethoxyphenoxy]ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine) and chlorethylclonidine each antagonized the positive inotropic effect of phenylephrine. On the other hand, only chlorethylclonidine significantly blocked the positive inotropic effect of tyramine. However, the presence of both antagonists was needed to block the positive inotropic effect elicited by the exogenous addition of the low concentration of noradrenaline. These data suggest that after extensive blockade of beta-adrenoceptors the positive inotropic effects of phenylephrine and exogenous noradrenaline result from stimulation of the alpha1A- and alpha1B-adrenoceptor subtypes, whereas that of endogenous noradrenaline is mediated via the alpha1B-adrenoceptor subtype. This could be explained by assuming that the alpha1B-adrenoceptor subtype population may be located on a space confronting more closely to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype population.
我们研究了介导去氧肾上腺素和去甲肾上腺素以及酪胺释放的内源性去甲肾上腺素在兔乳头肌中产生正性肌力作用的α1-肾上腺素能受体亚型。在普萘洛尔存在的情况下，去氧肾上腺素和酪胺均以浓度依赖性方式产生正性肌力作用。WB4101（N-[2-(2,6-二甲氧基苯氧基)乙基]-2,3-二氢-1,4-苯并二恶英-2-甲胺）和氯乙可乐定各自拮抗去氧肾上腺素的正性肌力作用。另一方面，只有氯乙可乐定能显著阻断酪胺的正性肌力作用。然而，需要同时存在这两种拮抗剂才能阻断外源性添加低浓度去甲肾上腺素所引发的正性肌力作用。这些数据表明，在广泛阻断β-肾上腺素能受体后，去氧肾上腺素和外源性去甲肾上腺素的正性肌力作用是由α1A-和α1B-肾上腺素能受体亚型的刺激所致，而内源性去甲肾上腺素的正性肌力作用是通过α1B-肾上腺素能受体亚型介导的。这可以通过假设α1B-肾上腺素能受体亚型群体可能比α1A-肾上腺素能受体亚型群体更靠近交感神经末梢的空间位置来解释。
