title: Lipophilic beta-adrenoceptor antagonists stimulate low density lipoprotein receptor activity in human skin fibroblasts.
abstract: The effect of beta-adrenoceptor antagonists on the receptor-mediated low density lipoprotein (LDL) binding and internalization was studied in vitro in human skin fibroblasts. The cellular uptake of 125I-labeled human LDL was dose dependently elevated by some, but not all, of the drugs used. This effect of beta-adrenoceptor antagonists was positively related to their lipophilicity, and was prevented by cycloheximide and by alpha-amanitin. Scatchard analysis of the saturable LDL binding indicates an increased number of LDL binding sites. Our studies show that the stimulating effect of beta-adrenoceptor 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 determinant 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.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000546:Amanitins / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D000546:Amanitins; D008077:Lipoproteins, LDL; D011412:Propanolamines; D011973:Receptors, LDL; C026777:ICI 118551; D003513:Cycloheximide