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.
Lipophilic β-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts / Corsini, A.; Bernini, F; Cighetti, G.; Soma, M.; Galli, G.; Fumagalli, R.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 36:12(1987), pp. 1901-1906. [10.1016/0006-2952(87)90486-2]
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