Han C, Yu G, Zhang Y, Xu K, Qu P, Dong E
Institute of Vascular Medicine, Third Hospital, Beijing Medical University, People's Republic of China.
Eur J Pharmacol. 1995 Dec 29;294(2-3):593-9. doi: 10.1016/0014-2999(95)00607-9.
Alterations in the cardiac alpha1-adrenoceptor and its subtypes in thyroxine-treated rats were studied by means of radioligand binding assays, measurement of contractile response and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that in thyroxine-treated rats the cardiac alpha1-adrenoceptor density (Bmax) was reduced from 51.6 +/- 6.0 fmol/mg in control to 40.9 +/- 3.7 fmol/mg (P<0.01); and the percentage of high affinity sites for 5-methyl-urapidil decreased from 23.3 +/- 2.0% in control to 10.8 +/- 2.0% in thyroxine-treated rats (P<0.05). The data indicated that the high-affinity sites for 5-methyl-urapidil (alpha1A-adrenoceptor) were reduced (from 12.0 to 4.4 fmol/mg), but the low-affinity sites for 5-methyl-urapidil (alpha1B- plus alpha1D-adrenoceptor) were not changed (from 39.6 to 36.5 fmol/mg). RT-PCR showed that steady-state levels of mRNA for alpha1A- and alpha1B-adrenoceptors were decreased, while that for alpha1D-adrenoceptor was raised in thyroxine-treated rats. In the isolated electrically driven left atria the phenylephrine-induced maximal contractions were reduced from 258 +/- 17 mg in control to 188 +/- 24 mg in thyroxine-treated rats (P<0.05). The pA2 values of 5-methyl-urapidil were reduced from 8.89 +/- 0.36 in control to the hyperthyroidism of 7.87 +/- 0.43 in thyroxine-treated rats (P<0.05). Chlorethylclonidine preincubation shifted concentration-response curves for phenylephrine to the right and reduced the maximal response to a lesser extent in thyroxine-treated rats than in control rats. Thus we concluded that the total number of cardiac alpha1-adrenoceptors is reduced in thyroxine-treated rats. The change is subtype selective, with alpha1A- and alpha1B-adrenoceptors being reduced in number and alpha1D-adrenoceptor being increased.
通过放射性配体结合试验、收缩反应测定以及逆转录-聚合酶链反应（RT-PCR），研究了甲状腺素处理大鼠心脏α1-肾上腺素能受体及其亚型的变化。结果显示，在甲状腺素处理的大鼠中，心脏α1-肾上腺素能受体密度（Bmax）从对照组的51.6±6.0 fmol/mg降至40.9±3.7 fmol/mg（P<0.01）；5-甲基尿嘧啶的高亲和力位点百分比从对照组的23.3±2.0%降至甲状腺素处理大鼠的10.8±2.0%（P<0.05）。数据表明，5-甲基尿嘧啶的高亲和力位点（α1A-肾上腺素能受体）减少（从12.0降至4.4 fmol/mg），而5-甲基尿嘧啶的低亲和力位点（α1B-加α1D-肾上腺素能受体）未改变（从39.6降至36.5 fmol/mg）。RT-PCR显示，甲状腺素处理大鼠中α1A-和α1B-肾上腺素能受体的mRNA稳态水平降低，而α1D-肾上腺素能受体的mRNA稳态水平升高。在离体电驱动左心房中，去氧肾上腺素诱导的最大收缩力从对照组的258±17 mg降至甲状腺素处理大鼠的188±24 mg（P<0.05）。5-甲基尿嘧啶的pA2值从对照组的8.89±0.36降至甲状腺素处理大鼠甲状腺功能亢进时的7.87±0.43（P<0.05）。氯乙可乐定预孵育使去氧肾上腺素的浓度-反应曲线右移，且在甲状腺素处理大鼠中比在对照大鼠中对最大反应的降低程度更小。因此，我们得出结论，甲状腺素处理的大鼠心脏α1-肾上腺素能受体总数减少。这种变化具有亚型选择性，α1A-和α1B-肾上腺素能受体数量减少，而α1D-肾上腺素能受体数量增加。
