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 language | English |
|---|---|
| Pages (from-to) | 1901-1906 |
| Number of pages | 6 |
| Journal | Biochemical Pharmacology |
| Volume | 36 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jun 15 1987 |
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ASJC Scopus subject areas
- Pharmacology
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Lipophilic β-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts. / Corsini, Alberto; Bernini, Franco; Cighetti, Giuliana; Soma, Maurizio; Galli, Giovanni; Fumagalli, Remo.
In: Biochemical Pharmacology, Vol. 36, No. 12, 15.06.1987, p. 1901-1906.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lipophilic β-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts
AU - Corsini, Alberto
AU - Bernini, Franco
AU - Cighetti, Giuliana
AU - Soma, Maurizio
AU - Galli, Giovanni
AU - Fumagalli, Remo
PY - 1987/6/15
Y1 - 1987/6/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0023276801&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(87)90486-2
DO - 10.1016/0006-2952(87)90486-2
M3 - Article
C2 - 2885001
AN - SCOPUS:0023276801
VL - 36
SP - 1901
EP - 1906
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 12
ER -