Roscher A A, Wiesmann U N, Honegger U E
J Pharmacol Exp Ther. 1981 Feb;216(2):419-24.
Submaxillary glands of rats, chronically treated with isoproterenol or reserpine undergo morphological and functional alterations. These changes have been described to resemble those seen in human cystic fibrosis. Since it has been proposed that the beta adrenergic-mediated response is altered in exocrine glands of cystic fibrosis patients, we have examined whether the drug-induced alterations in rat salivary glands were accompanied by changes in the numbers and affinities of beta adrenergic receptor sites. Beta receptor characteristics were determined by means of direct binding studies with the beta adrenergic antagonist [3H]dihydroalprenolol. Compared to controls, specific binding capacities of [3H]dihydroalprenolol per unit of protein increased by 110 +/- 14% after reserpine treatment and decreased by 34 +/- 11% after isoproterenol administration (P less than .001). The difference in the number of receptor sites remained statistically significant whether expressed per gram of fresh weight or per unit of the membrane marker 5'-nucleotidase activity. Dissociation constants of the binding were not significantly different between the treatment groups. The observed changes in the number of beta receptors showed an inverse relationship to the drug-induced presumed changes of catecholamine concentrations at the receptor sites. This suggests the existence of a feedback system which maintains the balance within the autonomous nervous system. We speculate that in cystic fibrosis this adaptive system is genetically abnormal.
长期用异丙肾上腺素或利血平处理的大鼠颌下腺会发生形态和功能改变。这些变化被描述为类似于人类囊性纤维化中所见的变化。由于有人提出囊性纤维化患者外分泌腺中β肾上腺素能介导的反应发生改变,我们研究了药物诱导的大鼠唾液腺改变是否伴随着β肾上腺素能受体位点数量和亲和力的变化。通过与β肾上腺素能拮抗剂[3H]二氢阿普洛尔进行直接结合研究来确定β受体特征。与对照组相比,利血平处理后每单位蛋白质的[3H]二氢阿普洛尔特异性结合能力增加了110±14%,异丙肾上腺素给药后降低了34±11%(P<0.001)。无论以每克鲜重还是以单位膜标记物5'-核苷酸酶活性来表示,受体位点数量的差异在统计学上仍然显著。各处理组之间结合的解离常数没有显著差异。观察到的β受体数量变化与药物诱导的受体位点儿茶酚胺浓度的假定变化呈负相关。这表明存在一个维持自主神经系统内平衡的反馈系统。我们推测在囊性纤维化中这种适应性系统存在基因异常。