Gautheron P, Sugrue M F
Centre de Recherche, Merck Sharp & Dohme-Chibret, Riom, France.
Graefes Arch Clin Exp Ophthalmol. 1987;225(5):331-4. doi: 10.1007/BF02153399.
Topically administered salbutamol was extremely effective in suppressing immediate allergic conjunctivitis in the guinea pig; a dose as low as 0.1% elicited 98% inhibition. Topical pretreatment with 1% propranolol completely blocked the suppressant action of 0.1% salbutamol. This was also the case after systemic propranolol (1 mg/kg SC); the beta-adrenoceptor antagonist itself has no effect on antigen-induced inflammation. The effect of 0.1% salbutamol was unaltered by pretreatment with the specific beta 1-adrenoceptor antagonist betaxolol (1 mg/kg SC). In marked contrast, the suppressant action of 0.1% salbutamol was profoundly inhibited by pretreatment with the selective beta 2-adrenoceptor antagonist ICI-118,551 (0.5 mg/kg SC). The experiments employing beta-adrenoceptor antagonists unequivocally demonstrate that the salbutamol suppression of immediate allergic conjunctivitis in the guinea pig is mediated via the activation of beta 2-adrenoceptors. The methylxanthine phosphodiesterase inhibitor theophylline was active after oral administration, 50 mg/kg eliciting an 80% inhibition. Theophylline was inactive topically at 1% and 5%, but this could be due to the fact that the compound was insoluble at these concentrations. Thus, procedures that elevate cyclic-AMP levels suppress immediate hypersensitivity reactions in the guinea pig conjunctiva. Whether or nor this offers an alternative approach to treat allergic conjunctivitis in humans remains to be determined.
局部应用沙丁胺醇对抑制豚鼠速发型过敏性结膜炎极为有效;低至0.1%的剂量可产生98%的抑制作用。用1%普萘洛尔进行局部预处理可完全阻断0.1%沙丁胺醇的抑制作用。全身应用普萘洛尔(1mg/kg皮下注射)后也是如此;β-肾上腺素能受体拮抗剂本身对抗原诱导的炎症无作用。0.1%沙丁胺醇的作用不受特异性β1-肾上腺素能受体拮抗剂倍他洛尔(1mg/kg皮下注射)预处理的影响。形成鲜明对比的是,0.1%沙丁胺醇的抑制作用被选择性β2-肾上腺素能受体拮抗剂ICI-118,551(0.5mg/kg皮下注射)预处理显著抑制。使用β-肾上腺素能受体拮抗剂的实验明确表明,豚鼠速发型过敏性结膜炎中沙丁胺醇的抑制作用是通过β2-肾上腺素能受体的激活介导的。甲基黄嘌呤磷酸二酯酶抑制剂茶碱口服给药后有活性,50mg/kg可产生80%的抑制作用。茶碱在1%和5%浓度下局部应用无活性,但这可能是由于该化合物在这些浓度下不溶。因此,提高环磷酸腺苷水平的方法可抑制豚鼠结膜中的速发型超敏反应。这是否为治疗人类过敏性结膜炎提供了另一种方法仍有待确定。