1. Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts
- Author
-
Haruo Nakamura and M. Suzukawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ketanserin ,media_common.quotation_subject ,Reductase ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Internalization ,Cells, Cultured ,Skin ,media_common ,Pharmacology ,biology ,Cholesterol ,musculoskeletal, neural, and ocular physiology ,General Medicine ,Fibroblasts ,musculoskeletal system ,Hydroxymethylglutaryl-CoA reductase ,Up-Regulation ,Endocrinology ,Receptors, LDL ,Mechanism of action ,chemistry ,HMG-CoA reductase ,LDL receptor ,cardiovascular system ,biology.protein ,Hydroxymethylglutaryl CoA Reductases ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,medicine.drug - 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.
- Published
- 1990