Lipophilic beta-adrenoceptor antagonists stimulate low density lipoprotein receptor activity in human skin fibroblasts

The effect of (β-adrenoccptor antagonists on the rcccptor-mediated low density lipoprotein (LDL) binding and internalization w'as studied in vitro in human skin fibro-blasts. The cellular uptake of ^l25I-labeIcd human LDL was dose depcndcntly elevated by some, but not all, of the drugs used. This effect of (β-adrenoccptor antagonists was positively related to their lipophilicity, and was prevented by cycloheximide and by α-amanitin.Scatchard analysis of the saturable LDL binding indicates an increased number of LDL binding sites. Our studies show that the stimulating effect of (β-adrenoccptor antagonists on the high affinity LDL binding and internalization in human skin fibroblasts involves DNA transcription and new protein synthesis, and identify drug lipophilicity as a major determi-nant of this action. This effect could be relevant in vivo in adipose tissue which accumulates lipophilic drugs and derives its cholesterol mainly from circulating LDL.