Effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic blocking activity, on the low-density lipoprotein receptor in human skin fibroblasts.
To investigate the mechanisms of the hypolipidemic effect of monatepil, a new class of calcium antagonists with alpha 1-adrenergic blocking activity, we examined the effects of the drug on low-density lipoprotein (LDL) receptor activity and the level of LDL receptor mRNA present in cultured human skin fibroblasts. At concentrations of 2 x 10(-5) M, monatepil increased 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 x 10(-5) M of monatepil for 6 hours resulted in an increase in LDL receptor mRNA to 163% of the control level (n = 2), as shown by Northern blot analysis. Our results suggest that the hypolipidemic clinical effects of monatepil may be due to increased LDL receptor activity.
Matsunaga
A
A
Department of Internal Medicine, School of Medicine, Fukuoka University, Japan. matsunag@msat.fukuoka-u.ac.jp
Inoue
T
T
Koga
T
T
Mori
K
K
Kugi
M
M
Sasaki
J
J
Arakawa
K
K
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D015152:Blotting, Northern; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003988:Dibenzothiepins / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000187:drug effects*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D003988:Dibenzothiepins; D007457:Iodine Radioisotopes; D010879:Piperazines; D012333:RNA, Messenger; D011973:Receptors, LDL; D002784:Cholesterol; C067818:monatepil