Effects of Monatepil, a Novel Calcium Antagonist with α1-Adrenergic Blocking Activity, on the Low-Density Lipoprotein Receptor in Human Skin Fibroblasts.

To investigate the mechanisms of the hypolipidemic effect ofmonatepil, a new class of calcium antagonists withα₁-adrenergic blocking activity, we examined theeffects of the drug on low-density lipoprotein (LDL) receptor activity andthe level of LDL receptor mRNA present in cultured human skin fibroblasts.At concentrations of 2 × 10⁻⁵M, monatepilincreased the binding (248 ± 43% mean ± SD),internalization (374 ± 18%), and degradation (145 ±2%) of ¹²⁵I-LDL in human skin fibroblasts (n =3, p<0.05). Treatment of human skin fibroblasts with 2 × 10⁻⁵ M of monatepil for 6 hours resulted in an increasein LDL receptor mRNA to 163% of the control level (n = 2), asshown by Northern blot analysis. Our results suggest that the hypolipidemicclinical effects of monatepil may be due to increased LDL receptoractivity. [ABSTRACT FROM AUTHOR]