Effect of derivatives of trapidil on the expression of LDL receptors

The influence of trapidil and some of its derivatives (AR 12456, AR 12463, AR 12465) on the LDL receptor mediated uptake and degradation of 125 I-LDL by human skin fibroblasts (HSF) and human hepatic cells (HEP G2) was investigated. AR 12456 enhanced the uptake and degradation of 125 I-LDL in HEP G2, but inhibited this pathway in HSF. When this drug was preincubated with HEP G2 cells, and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. Trapidil, AR 12463 and AR 12465 were inactive under the same experimental conditions. These findings suggest that a metabolite of AR 12456 might be responsible for the enhanced expression of LDL receptors in human cells.