Botana L M, Espinosa J, Eleno N
Gen Pharmacol. 1987;18(2):141-8. doi: 10.1016/0306-3623(87)90240-0.
Adrenergic agonists inhibit the release of histamine from rat pleural and peritoneal mast cells stimulated with compound 48/80 to a degree dependent on their beta-activity. Isoprenaline takes part in a stereoselective inhibitory action in the range 10(-7)-10(-4) M. Adrenaline induces a similar response pattern, with inhibition at higher concentrations. The response profile, but not the maximum values of inhibition, is clearly dependent on the concentration of the histamine releaser. Noradrenaline by itself is a histamine releaser, no stereoselectivity being observed. In the presence of compound 48/80 it takes part in a non-stereoselective inhibitory reaction at low concentrations. Inhibition of histamine release by isoprenaline was antagonized by 10 or 100 microM propranolol except at the highest isoprenaline concentration (1 mM). Both atenolol and propranolol nullified the inhibitory activity of noradrenaline, but not the increased histamine release it induces at higher concentrations (at least when acting in conjunction with compound 48/80). When rat mast cells are purified through Percoll, a change in their response profiles is observed. Isoprenaline and adrenaline by themselves elicit non-specific release of histamine; with compound 48/80, release is additive in the case of isoprenaline and supra-additive in the case of adrenaline. Results point to the loss of beta-adrenergic inhibitory activity after purification.
肾上腺素能激动剂可抑制由化合物48/80刺激的大鼠胸膜和腹膜肥大细胞释放组胺,其抑制程度取决于它们的β活性。异丙肾上腺素在10(-7)-10(-4)M范围内发挥立体选择性抑制作用。肾上腺素诱导类似的反应模式,在较高浓度时产生抑制作用。反应曲线,但不是最大抑制值,明显取决于组胺释放剂的浓度。去甲肾上腺素本身是一种组胺释放剂,未观察到立体选择性。在存在化合物48/80的情况下,它在低浓度时参与非立体选择性抑制反应。除了在最高异丙肾上腺素浓度(1mM)时,10或100μM普萘洛尔可拮抗异丙肾上腺素对组胺释放的抑制作用。阿替洛尔和普萘洛尔均消除了去甲肾上腺素的抑制活性,但未消除其在较高浓度时诱导的组胺释放增加(至少在与化合物48/80共同作用时)。当通过Percoll纯化大鼠肥大细胞时,观察到它们的反应曲线发生变化。异丙肾上腺素和肾上腺素本身会引起组胺的非特异性释放;对于化合物48/80,异丙肾上腺素的释放是相加的,而肾上腺素的释放是超相加的。结果表明纯化后β肾上腺素能抑制活性丧失。