Aarons R D, Molinoff P B
J Pharmacol Exp Ther. 1982 May;221(2):439-43.
Abrupt withdrawal after the chronic administration of propranolol results in clinical syndromes that suggest adrenergic hypersensitivity. Furthermore, propranolol administration has been shown to lead to an increase in the density of beta adrenergic receptors on human lymphocytes. The present studies were designed to assess the relevance of changes measured in lymphocytes to changes that may occur in solid tissues. Direct measurement of the density and properties of beta adrenergic receptors in membrane fragments was performed in vitro using the radioligand [125I]iodohydroxybenzylpindolol. Chronic infusion of propranolol by s.c. implanted osmotic minipumps generated sustained plasma concentrations of propranolol sufficient to cause chronic blockade of beta adrenergic receptors. Infusion of propranolol for 7 days resulted in significant increases in the density of beta adrenergic receptors in rat ventricles, lungs and lymphocytes. A computer-assisted graphic analysis of results obtained in studies with drugs selective for beta-1 or beta-2 receptors revealed increases in the densities of both beta-1 an beta-2 adrenergic receptors. These results are consistent with the hypothesis that change in beta adrenergic receptors on lymphocytes are qualitatively similar to alterations in beta adrenergic receptors in solid tissues not routinely accessible in humans. Increases in the densities of beta-1 and/or beta-2 adrenergic receptors in solid tissues may be related to some of the untoward effects observed in humans after abrupt discontinuation of propranolol administration.
长期服用普萘洛尔后突然停药会引发一些临床综合征，提示肾上腺素能超敏反应。此外，研究表明，服用普萘洛尔会导致人淋巴细胞上β肾上腺素能受体密度增加。本研究旨在评估淋巴细胞中所测变化与实体组织中可能发生的变化之间的相关性。使用放射性配体[125I]碘羟基苄基吲哚洛尔在体外对膜碎片中的β肾上腺素能受体密度和特性进行直接测量。通过皮下植入渗透微型泵长期输注普萘洛尔，可使血浆中普萘洛尔浓度持续维持在足以导致β肾上腺素能受体长期阻滞的水平。输注普萘洛尔7天可导致大鼠心室、肺和淋巴细胞中β肾上腺素能受体密度显著增加。对使用β-1或β-2受体选择性药物的研究结果进行计算机辅助图形分析发现，β-1和β-2肾上腺素能受体密度均增加。这些结果与以下假设一致，即淋巴细胞上β肾上腺素能受体的变化在性质上与人体中通常难以获取的实体组织中β肾上腺素能受体的改变相似。实体组织中β-1和/或β-2肾上腺素能受体密度的增加可能与人类在突然停用普萘洛尔后观察到的一些不良反应有关。
