Summary
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.
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Suzukawa, M., Nakamura, H. Effect of ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts. Eur J Clin Pharmacol 39, 217–220 (1990). https://doi.org/10.1007/BF00315099
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DOI: https://doi.org/10.1007/BF00315099