Daffonchio L, Hernandez A, Brunelli G, Omini C
Institute of Pharmacological Sciences, University of Milan, Italy.
Pulm Pharmacol. 1989;1(4):161-5. doi: 10.1016/s0952-0600(89)80012-2.
The occurrence of beta-adrenoceptor desensitisation in clinical experience, after long term therapy with specific beta 2-agonists, is still an open question, even if this phenomenon is easily observed in different experimental models. Since the majority of these experiments have been performed in normal animals, we investigated the possible occurrence of beta-adrenoceptor desensitisation in the ovalbumin actively sensitised guinea-pig model of experimental asthma. The isoproterenol concentration-response curves performed in pilocarpine contracted guinea-pig trachea in vitro were shifted to the right by the beta-adrenoceptor desensitisation procedure, which was achieved by the in vitro administration of isoproterenol (10(-5) M x 2 times x 20 min each) both in normal and ovalbumin sensitised tissues. The same desensitisation procedure markedly affected epinephrine-relaxing capacity in both normal and ovalbumin actively sensitised guinea-pig tracheae. However, the ovalbumin sensitised tissue seemed to be more sensitive than normal to the specific beta 2-agonist procaterol; in parallel the beta 2-mediated relaxation was more impaired by isoproterenol-induced beta-adrenoceptor down regulation in ovalbumin sensitised trachea when compared to normal. Similar results have been obtained using salbutamol as the beta 2-adrenoceptor desensitising agent. The changes in beta-adrenoceptor reactivity between normal and ovalbumin sensitised guinea-pig tracheae seemed to depend on the active sensitisation process. No difference in the degree of beta-adrenoceptor down regulation was observed in passively ovalbumin sensitised guinea-pig trachea as compared to normal. These data suggest that, in this model of experimental asthma, beta-adrenoceptor reactivity is in some way modified and that this phenomenon might contribute to the genesis of asthma.
在临床实践中，长期使用特定的β2激动剂后是否会发生β肾上腺素能受体脱敏现象，仍然是一个悬而未决的问题，尽管在不同的实验模型中很容易观察到这种现象。由于大多数此类实验是在正常动物身上进行的，我们研究了在卵清蛋白主动致敏的实验性哮喘豚鼠模型中β肾上腺素能受体脱敏现象的可能发生情况。在体外对毛果芸香碱收缩的豚鼠气管进行异丙肾上腺素浓度-反应曲线实验时，无论是正常组织还是卵清蛋白致敏组织，通过体外给予异丙肾上腺素（10^(-5)M，每次2次，每次20分钟）实现的β肾上腺素能受体脱敏程序都会使曲线右移。相同的脱敏程序对正常和卵清蛋白主动致敏的豚鼠气管中肾上腺素的舒张能力均有显著影响。然而，卵清蛋白致敏组织似乎比正常组织对特异性β2激动剂丙卡特罗更敏感；与此同时，与正常组织相比，异丙肾上腺素诱导的β肾上腺素能受体下调在卵清蛋白致敏气管中对β2介导的舒张作用的损害更大。使用沙丁胺醇作为β2肾上腺素能受体脱敏剂也得到了类似的结果。正常和卵清蛋白致敏的豚鼠气管之间β肾上腺素能受体反应性的变化似乎取决于主动致敏过程。与正常情况相比，在被动卵清蛋白致敏的豚鼠气管中未观察到β肾上腺素能受体下调程度的差异。这些数据表明，在这个实验性哮喘模型中，β肾上腺素能受体反应性在某种程度上发生了改变，并且这种现象可能有助于哮喘的发生。
