Middleton A, Middleton B
Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.
Biochem J. 1990 May 1;267(3):607-14. doi: 10.1042/bj2670607.
Receptor-mediated binding and metabolism of low-density lipoproteins (LDL) in cultured human vascular smooth-muscle cells and skin fibroblasts are altered by increased cellular cyclic AMP concentrations. However, the LDL receptor does not respond to changes in cyclic AMP concentration in a simple manner. The activation of adenylate cyclase with forskolin, or the addition of membrane-permeant cyclic AMP analogues, initially decreases the expression of the LDL receptor, but is followed by a substantial increase in receptor expression after 24 h. This increase does not occur in the presence of inhibitors of RNA or protein synthesis, and is due to doubling of the Bmax. of the LDL receptor, without alteration of its affinity for LDL. By contrast, elevation of cyclic AMP concentration by inhibition of phosphodiesterases results in decreased receptor expression throughout the 24 h period. These two response patterns are reproducible phenomena, consistently observed in low-passaged cells derived from seven unrelated individuals.
细胞内环磷酸腺苷（cAMP）浓度升高会改变培养的人血管平滑肌细胞和皮肤成纤维细胞中受体介导的低密度脂蛋白（LDL）结合及代谢。然而，LDL受体对cAMP浓度变化的反应并非简单直接。用福司可林激活腺苷酸环化酶，或添加可透过细胞膜的cAMP类似物，最初会降低LDL受体的表达，但24小时后受体表达会大幅增加。在存在RNA或蛋白质合成抑制剂的情况下，这种增加不会发生，且这是由于LDL受体的最大结合容量（Bmax）翻倍，而其对LDL的亲和力并未改变。相比之下，通过抑制磷酸二酯酶提高cAMP浓度会导致在整个24小时期间受体表达降低。这两种反应模式是可重复的现象，在来自七个无关个体的低代细胞中一直观察到。
