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Arenberger P, Raap A, Armah B, Kemeny L, Ruzicka T: 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. Skin Pharmacol. 1993;6(2):148-51.
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. |
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