Different changes of plasma membrane β-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol
Different changes of plasma membrane β-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol
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DOI：
10.1016/j.lfs.2007.06.003
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发表时间：
2007-07-12
期刊：
影响因子：
6.1
通讯作者：
Muramatsu, Ikunobu
中科院分区：
文献类型：
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作者：
Horinouchi, Takahiro;Morishima, Shigeru;Muramatsu, Ikunobu
最近，亲水性放射性配体[H-3]-CGP12177的组织片段结合方法被开发出来用于检测大鼠心脏质膜β-肾上腺素受体(Horinouchi等人，2006年)。本研究分别给予大鼠心得安(40 mg·kg~(-1)·d~(-1))、阿替洛尔(40 mg·kg~(-1)·d~(-1))和贝凡洛尔(200 mg·kg~(-1)·d~(-1))灌胃6周，观察心肌细胞质膜β-肾上腺素能受体及其基因表达的变化。长期服用心得安可增加β(1)-肾上腺素能受体，减少β(2)-肾上腺素能受体，但不改变质膜β-肾上腺素能受体的总量。阿替洛尔增加质膜β(1)-和β(2)-肾上腺素能受体，而贝凡洛尔对β-受体密度及其亚型比例无影响。相反，在传统的匀浆结合实验中检测到的β受体密度极低(用组织片段结合法检测到约60%的质膜β受体)，长期服用β受体拮抗剂的效果不一定与质膜β受体一致。心得安不影响β(1)-和β(2)-肾上腺素能受体的基因表达水平，而阿替洛尔或贝凡洛尔能显著降低β(1)-肾上腺素能受体的基因表达水平，但不影响β(2)-肾上腺素能受体的基因表达水平。目前对完整组织节段的结合研究清楚地表明，与匀浆结合部位和mRNA水平相比，大鼠心脏质膜β(1)和β(2)受体受到三种β受体拮抗剂慢性处理的不同影响；心得安分别上调和下调β(1)和β(2)受体，阿替洛尔上调这两种亚型，但贝凡洛尔对这两种亚型的影响不明显。(C)2007 Elsevier Inc.保留所有权利。
Recently, tissue segment binding method with a hydrophilic radioligand [H-3]-CGP12177 was developed to detect plasma membrane beta-adrenoceptors in rat heart (Horinouchi et al., 2006). In the present study, propranolol (40 mg kg(-1) day(-1)), atenolol (40 mg kg-(1) day(-1)) and bevantolol (200 mg kg(-1) day(-1)) were administered to rats for 6 weeks, and the changes of plasma membrane beta-adrenoceptors and their mRNA expression in rat ventricle were examined. Chronic administration of propranolol increased the beta(1)-adrenoceptors but decreased the beta(2)-adrenoceptors without changing total amount of plasma membrane beta-adrenoceptors. Atenolol increased both plasma membrane beta(1)- and beta(2)-adrenoceptors, whereas bevantolol had no effect on the beta-adrenoceptor density and their subtype proportions. In contrast, the density of beta-adrenoceptors detected in conventional homogenate binding study was extremely low (approximately 60% of plasma membrane beta-adrenoceptors detected with the tissue segment binding method) and the effects of chronic administration of p-adrenoceptor antagonists were not necessarily in accord with those at the plasma membrane beta-adrenoceptors. The mRNA levels of beta(1)- and beta(2)-adrenoceptors were not altered by propranolol treatment, while beta(1)-adrenoceptor mRNA significantly decreased after administration of atenolol or bevantolol without changing the level of beta(2)-adrenoceptor mRNA. The present binding study with intact tissue segments clearly shows that the plasma membrane beta(1)- and beta(2)-adrenoceptors of rat heart, in contrast to the homogenate binding sites and the mRNA levels, are differently affected by chronic treatment with three beta-adrenoceptor antagonists; up- and down-regulations of beta(1)- and beta(2)-adrenoceptors, respectively, by propranolol, and up-regulation of both the subtypes by atenotol, but no significant change in both the subtypes by bevantolol. (c) 2007 Elsevier Inc. All rights reserved.