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Upregulation of beta(1)-adrenergic receptors in ovariectomized rat hearts

机译:去卵巢大鼠心脏中β(1)-肾上腺素受体的上调

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Changes in cardiac myofilament Ca2+ activation have been demonstrated in ovariectomized rats. The underlying mechanisms responsible for these changes, however, are unknown. Accordingly, we measured both density and binding affinity of cardiac beta(1)-adrenergic receptors in sarcolemmal preparations from 10-week ovariectomized rats, pair-fed ovariectomized rats, and sham-operated control rats. Receptor protein content was also measured by immunoblotting. Deprivation of ovarian sex hormones for 10 weeks induced a significant upregulation of beta(1)-adrenergic receptors without affecting binding affinity. The same magnitude of receptor upregulation was also detected in pair-fed ovariectomized hearts. To determine which hormone is responsible for the observed increase in beta(1)-adrenergic receptor density, various sex hormone supplemental regimens were administered to ovariectomized rats. Subcutaneous injection of estrogen (5 mug/rat), progesterone (1 mg/rat), or estrogen plus progesterone three times a week all effectively prevented the upregulation of the beta(1)-adrenoceptors. Western blot analyses using polyclonal antibody of beta(1)-adrenergic receptors revealed the same pattern of changes in the protein content of the receptors in these various groups of experimental hearts as those obtained from the receptor binding assay. These results suggest a possible direct suppressive effect of ovarian sex hormones on the expression of cardiac beta(1)-adrenergic receptors. (C) 2003 Elsevier Science Inc. All rights reserved. [References: 41]
机译:已经在去卵巢的大鼠中证实了心肌细丝Ca 2+活化的变化。然而,导致这些变化的潜在机制尚不清楚。因此,我们测量了10周去卵巢大鼠,成对喂养的去卵巢大鼠和假手术对照大鼠的肌膜制剂中心脏β(1)-肾上腺素受体的密度和结合亲和力。受体蛋白含量也通过免疫印迹法测量。剥夺卵巢性激素10周诱导了beta(1)-肾上腺素受体的显着上调而不影响结合亲和力。在配对喂养的去卵巢心脏中也检测到了相同程度的受体上调。为了确定哪种激素是导致观察到的β(1)-肾上腺素受体密度增加的原因,向卵巢切除的大鼠施用了各种性激素补充方案。每周三次皮下注射雌激素(5杯/大鼠),孕酮(1 mg /大鼠)或雌激素加孕酮均有效地阻止了β(1)-肾上腺素受体的上调。使用β(1)-肾上腺素受体多克隆抗体的蛋白质印迹分析显示,在这些实验心脏的各个不同组中,受体蛋白质含量的变化与从受体结合测定法获得的蛋白质变化相同。这些结果表明,卵巢性激素可能直接抑制心脏β(1)-肾上腺素能受体的表达。 (C)2003 Elsevier Science Inc.保留所有权利。 [参考:41]

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