Inagaki N, Kawasaki H, Hiyama H, Goto M, Matsuo A, Nagai H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Eur J Pharmacol. 1997 Oct 8;336(2-3):225-31. doi: 10.1016/s0014-2999(97)01247-8.
Inhibitory mechanisms of isoproterenol and clenbuterol for immunoglobulin E (IgE)-mediated experimental allergic reactions in rats were studied. IgE-mediated passive cutaneous anaphylaxis, histamine-induced cutaneous reaction and serotonin-induced cutaneous reaction were evoked at the same time in the same rats. Isoproterenol administered intravenously immediately before challenge inhibited all these reactions significantly. Clenbuterol administered intravenously 0-3 h before challenge also significantly inhibited the three cutaneous reactions. The inhibition was maximum when the drug was given 1 h before challenge. Passive cutaneous anaphylaxis was always inhibited more potently than histamine-induced cutaneous reaction and serotonin-induced cutaneous reaction by these beta-adrenoceptor agonists. Passive peritoneal anaphylaxis was caused by injecting an antigen intravenously. Isoproterenol administered intravenously immediately before challenge inhibited the reaction significantly. Clenbuterol administered intravenously 0-3 h before challenge also significantly inhibited passive peritoneal anaphylaxis, maximally so when given 1 h before challenge. In vitro IgE-dependent histamine release from sensitized peritoneal mast cells or mesenteric mast cells was not affected by isoproterenol and clenbuterol. Mouse monoclonal IgE, a foreign protein, administered intravenously decreased rapidly in the circulation. About 50% of the mouse IgE given disappeared in 20 min. The decrease of mouse IgE was partly but significantly inhibited by the beta-adrenoceptor agonists, and the inhibition was abolished by simultaneous treatment with propranolol. These results indicate that direct inhibition of mast cell activation does not contribute to the potent inhibition of in vivo allergic reactions in rats by beta-adrenoceptor agonists, and that inhibition of the allergic cutaneous reaction is partially explained by the inhibition of vascular permeability increases caused by mast cell mediators. Penetration of intravenously administered antigen from blood vessels to peripheral tissues to cause mast cell activation might be inhibited by beta-adrenoceptor agonists, and this could play some role in inhibiting intravenous antigen-induced allergic reactions in rats. Clenbuterol exhibited its maximum action with some latency in vivo, suggesting that some time-requiring process may be involved in the manifestation of its action.
研究了异丙肾上腺素和克伦特罗对大鼠免疫球蛋白E（IgE）介导的实验性过敏反应的抑制机制。在同一大鼠中同时引发IgE介导的被动皮肤过敏反应、组胺诱导的皮肤反应和血清素诱导的皮肤反应。在激发前立即静脉注射异丙肾上腺素可显著抑制所有这些反应。在激发前0 - 3小时静脉注射克伦特罗也显著抑制了这三种皮肤反应。当在激发前1小时给药时，抑制作用最大。这些β-肾上腺素能受体激动剂对被动皮肤过敏反应的抑制作用总是比对组胺诱导的皮肤反应和血清素诱导的皮肤反应更强。被动腹膜过敏反应是通过静脉注射抗原引起的。在激发前立即静脉注射异丙肾上腺素可显著抑制该反应。在激发前0 - 3小时静脉注射克伦特罗也显著抑制被动腹膜过敏反应，在激发前1小时给药时抑制作用最大。异丙肾上腺素和克伦特罗对体外致敏腹膜肥大细胞或肠系膜肥大细胞依赖IgE的组胺释放没有影响。静脉注射的小鼠单克隆IgE（一种外来蛋白质）在循环中迅速减少。注射的小鼠IgE约50%在20分钟内消失。β-肾上腺素能受体激动剂部分但显著地抑制了小鼠IgE的减少，并且用普萘洛尔同时处理可消除这种抑制作用。这些结果表明，β-肾上腺素能受体激动剂对大鼠体内过敏反应的有效抑制并非直接通过抑制肥大细胞活化实现，并且过敏皮肤反应的抑制部分可归因于对肥大细胞介质引起的血管通透性增加的抑制。β-肾上腺素能受体激动剂可能抑制静脉注射的抗原从血管渗透到外周组织以激活肥大细胞，这可能在抑制大鼠静脉注射抗原诱导的过敏反应中起一定作用。克伦特罗在体内表现出最大作用有一定延迟，表明其作用的表现可能涉及一些需要时间的过程。
