Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts.
In man ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that ketanserin induces up-regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by ketanserin.
Suzukawa
M
M
1st Department of Internal Medicine, National Defence Medical College, Saitama, Japan.
Nakamura
H
H
D000328:Adult; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005347:Fibroblasts; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects
D011973:Receptors, LDL; D002784:Cholesterol; D007650:Ketanserin; D006903:Hydroxymethylglutaryl CoA Reductases