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 BETA-ADRENOCEPTOR ANTAGONISTS STIMULATE CHOLESTEROL-BIOSYNTHESIS IN HUMAN-SKIN FIBROBLASTS / A. CORSINI, F. BERNINI, G. CIGHETTI, M. SOMA, G. GALLI, R. FUMAGALLI. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 36:12(1987), pp. 1901-1906.

LIPOPHILIC BETA-ADRENOCEPTOR ANTAGONISTS STIMULATE CHOLESTEROL-BIOSYNTHESIS IN HUMAN-SKIN FIBROBLASTS

A. CORSINI
Primo
;
G. CIGHETTI;
1987

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.
Settore BIO/10 - Biochimica
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/191236
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