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.
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 assumed 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(-5) M 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 levels.
Department of Dermatology, University of Munich, FRG.
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P
Arenberger
A
A
Raap
B
B
Armah
L
L
Kemény
T
T
Ruzicka
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D018055:Receptors, Eicosanoid; D012878:Skin Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured
C066652:12-hydroxyeicosatetraenoic acid receptor; D006893:Hydroxyeicosatetraenoic Acids; D009284:Naphthols; D011956:Receptors, Cell Surface; D018055:Receptors, Eicosanoid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C061316:2-(phenylmethyl)-1-naphthol