Ghosh S, Liu M S
J Surg Res. 1983 Mar;34(3):239-45. doi: 10.1016/0022-4804(83)90066-5.
The effects of endotoxin administration on alpha-adrenergic receptors in dog liver plasma membranes were studied using [3H]dihydroergocryptine as a radioactive ligand. The Scatchard analysis revealed a two-component binding characteristic both in control and endotoxin-injected dogs. The Kd (dissociation constant) of the high-affinity component was increased by 32.5% (0.4 +/- 0.04 nM for control vs 0.53 +/- 0.06 nM for endotoxic; P less than 0.05) with no significant change in the Kd for the low-affinity component (3.0 +/- 0.44 nM for control vs 3.4 +/- 0.44 nM for endotoxic) 2 hr following endotoxin administration. The maximum binding capacity of the high-affinity component was decreased by 38.1% (460 +/- 19.3 and 285 +/- 14.8 fmole/mg protein for control and endotoxic, respectively; P less than 0.01) and that of the low-affinity component was decreased by 34.2% (1050 +/- 66.4 and 690 +/- 44.6 fmole/mg protein for control and endotoxic, respectively; P less than 0.05) 2 hr after endotoxin injection. The competitive inhibition studies show that the apparent Kd values for (-)-epinephrine, (-)-norepinephrine, and prazosin were increased 15, 13, and 25 times, respectively, with no significant change in the apparent Kd values for yohimbine or phentolamine 2 hr postendotoxin. These data demonstrate that the binding affinity of the high-affinity component and the number of alpha-adrenergic receptor binding sites were decreased in endotoxic shock. A modification of the alpha-adrenergic receptors in dog livers induced by endotoxin administration may play an important role in the development of hepatic glucose dyshomeostasis during shock.
以内毒素给予狗肝细胞膜上的α - 肾上腺素能受体的作用，使用[3H]二氢麦角隐亭作为放射性配体进行了研究。Scatchard分析显示，在对照狗和注射内毒素的狗中均呈现双组分结合特征。给予内毒素2小时后，高亲和力组分的解离常数（Kd）增加了32.5%（对照为0.4±0.04 nM，内毒素组为0.53±0.06 nM；P<0.05），而低亲和力组分的Kd无显著变化（对照为3.0±0.44 nM，内毒素组为3.4±0.44 nM）。高亲和力组分的最大结合容量降低了38.1%（对照和内毒素组分别为460±19.3和285±14.8 fmol/mg蛋白质；P<0.01），低亲和力组分的最大结合容量降低了34.2%（对照和内毒素组分别为1050±66.4和690±44.6 fmol/mg蛋白质；P<0.05），于内毒素注射后2小时出现。竞争性抑制研究表明，内毒素给药2小时后，（-）-肾上腺素、（-）-去甲肾上腺素和哌唑嗪的表观Kd值分别增加了15、13和25倍，而育亨宾或酚妥拉明的表观Kd值无显著变化。这些数据表明，内毒素休克时高亲和力组分的结合亲和力和α - 肾上腺素能受体结合位点数量减少。内毒素给药诱导的狗肝脏中α - 肾上腺素能受体的改变可能在休克期间肝葡萄糖稳态失衡的发生中起重要作用。
