Lipophilic β-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts

Alberto Corsini, Franco Bernini, Giuliana Cighetti, Maurizio Soma, Giovanni Galli, Remo Fumagalli

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of a series of β-adrenoceptor antagonists on cholesterol biosynthesis was studied in vitro in normal human skin fibroblasts. Some, but not all, of the drugs studied stimulated the incorporation of [2-14C]-acetate into cell sterols in a dose-dependent manner. This effect was unrelated to β-blocking potency, selectivity for β1 or β2 adrenoceptors and partial agonistic activity of the drugs, thus ruling out a β-receptor mediated mechanism. A positive, statistically significant correlation was found, however, between the drug lipophilicity and the stimulation of sterol biosynthesis. Propranolol, the most effective agent in increasing [2-14C]-acetate incorporation into cellular sterols, also enhanced the conversion of 3-hydroxy-3-methylglutaryl CoA (HMGCoA) into mevalonic acid, suggesting an interference of lipophilic β-adrenoceptor antagonists with HMHCoA-reductase, the feed-back regulated rate limiting step of cholesterol biosynthesis.

Original languageEnglish
Pages (from-to)1901-1906
Number of pages6
JournalBiochemical Pharmacology
Volume36
Issue number12
DOIs
Publication statusPublished - Jun 15 1987

ASJC Scopus subject areas

  • Pharmacology

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