The Lipoxygenase Inhibitor 2-Phenylmethyl-1-Naphthol (DuP 654) Is a 12(S)-Hydroxyeicosatetraenoic Acid Receptor Antagonist in the Human Epidermal Cell Line SCL-II
作者:
Petr Arenberger,
Achim Raap,
Benjamin Armah,
Lajos Kemény,
Thomas Ruzicka,
期刊:
Skin Pharmacology and Physiology
(Karger Available online 1993)
卷期:
Volume 6,
issue 2
页码: 148-151
ISSN:1660-5527
年代: 1993
DOI:10.1159/000211099
出版商: S. Karger AG
关键词: Keratinocyte;12-HETE binding;DuP 654
数据来源: Karger
摘要:
The lipoxygenase inhibitor 2-phenylmethyl-1 -naphthol (DuP 654) has been shown to be an active anti-inflammatory drug in a murine skin inflammation model. Since 12-HETE is as-sumed to have a pathophysiological role in inflammatory skin diseases, and epidermal cells possess high affinity binding sites for 12(S)-HETE, we studied the effect of DuP 654 on 12(S)-HETE binding to the human epidermal cell line SCL-II. DuP 654 antagonized 12(S)-HETE binding in a dose-dependent manner with a Ki of 3.41 ± 0.23 nM. The antagonistic effect was reversible. After 1- and 24-hour preincubation, the drug had no more significant inhibitory effect at concentrations between 10-10 and 10-5M on specific 12(S)-HETE binding (Bmax of 215,000 ± 21,000 receptors per cell) or on receptor affinity (Kd of 3.25 ± 0.42 nM). Our results show that DuP 654, in addition to its 5-lipoxygenase inhibitory activity, exhibits 12-HETE receptor antagonist effect, and therefore may be of benefit in skin diseases with elevated 12-HETE leve
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