title: Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts.
abstract: 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.
authors: 1st Department of Internal Medicine, National Defence Medical College, Saitama, Japan.
authors: M
authors: M
authors: Suzukawa
authors: H
authors: H
authors: Nakamura
mesh_terms: 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
chemical_list: D011973:Receptors, LDL; D002784:Cholesterol; D007650:Ketanserin; D006903:Hydroxymethylglutaryl CoA Reductases