Hawthorn M H, Broadley K J
Eur J Pharmacol. 1984 Oct 15;105(3-4):245-55. doi: 10.1016/0014-2999(84)90616-2.
This study was undertaken to determine whether reserpine-induced supersensitivity occurs in tissues containing beta1-adrenoceptors and in those with beta 2-adrenoceptors. Guinea-pigs and rats were pretreated with reserpine for either 3 days (5 mg kg-1 i.p. at 72 h, 3 mg kg-1 at 48 h and 3 mg kg-1 at 24 h before use) or 7 days (1 mg kg-1 daily). The sensitivities of left and right atria, papillary muscles, tracheal spirals, lung strips and uteri to isoprenaline were compared with those from untreated animals. The positive inotropic responses of left atria and papillary muscles and chronotropic responses of right atria from reserpine-pretreated animals were supersensitive to isoprenaline, the concentration-response curves being to the left. The relaxation response of the carbachol-contracted trachea also exhibited supersensitivity, but to a lesser extent. However, no supersensitivity occurred for the relaxation of carbachol-contracted lungs, K+-depolarized guinea-pig uteri or electrically stimulated rat uteri. As a pharmacological index of the presence of releasable noradrenergic stores, tyramine was added cumulatively to each tissue. Only cardiac and tracheal preparations yielded substantial responses, indicating the presence of sympathetic innervation. A relaxation of the rat uterus by tyramine was not attributable to releasable noradrenaline stores. The supersensitivity of the heart and trachea could therefore be associated with their sympathetic innervation and with the fact that their responses are mediated via beta 1-adrenoceptors; the trachea containing a small proportion of beta 1-adrenoceptors. The responses of the lung and uterus, however, are beta 2-adrenoceptor-mediated and failed to exhibit supersensitivity. Since the supersensitivity is a consequence of the neuronal depleting action of reserpine, these results are compatible with the concept that beta 1-adrenoceptors are associated with sympathetic innervation whereas beta 2-adrenoceptors are not.
本研究旨在确定利血平诱导的超敏反应是否发生在含有β1肾上腺素能受体的组织以及含有β2肾上腺素能受体的组织中。豚鼠和大鼠用利血平预处理3天（使用前72小时腹腔注射5 mg/kg，48小时注射3 mg/kg，24小时注射3 mg/kg）或7天（每日1 mg/kg）。将左、右心房、乳头肌、气管螺旋条、肺条和子宫对异丙肾上腺素的敏感性与未处理动物的进行比较。利血平预处理动物的左心房和乳头肌的正性变力反应以及右心房的变时反应对异丙肾上腺素超敏，浓度-反应曲线向左移。卡巴胆碱收缩的气管的舒张反应也表现出超敏，但程度较小。然而，卡巴胆碱收缩的肺、钾离子去极化的豚鼠子宫或电刺激的大鼠子宫的舒张未出现超敏。作为可释放去甲肾上腺素能储存存在的药理学指标，将酪胺累积添加到每个组织中。只有心脏和气管制剂产生明显反应，表明存在交感神经支配。酪胺对大鼠子宫的舒张作用并非归因于可释放的去甲肾上腺素能储存。因此，心脏和气管的超敏可能与其交感神经支配以及它们的反应通过β1肾上腺素能受体介导有关；气管含有少量β1肾上腺素能受体。然而，肺和子宫的反应是由β2肾上腺素能受体介导的，未表现出超敏。由于超敏是利血平的神经元耗竭作用的结果，这些结果与β1肾上腺素能受体与交感神经支配相关而β2肾上腺素能受体不相关的概念相符。
