Abstract |
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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Authors | P Arenberger, A Raap, B Armah, L Kemény, T Ruzicka |
Journal | Skin pharmacology : the official journal of the Skin Pharmacology Society
(Skin Pharmacol)
Vol. 6
Issue 2
Pg. 148-51
( 1993)
ISSN: 1011-0283 [Print] Switzerland |
PMID | 8394724
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 12-hydroxyeicosatetraenoic acid receptor
- Hydroxyeicosatetraenoic Acids
- Naphthols
- Receptors, Cell Surface
- Receptors, Eicosanoid
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
- 2-(phenylmethyl)-1-naphthol
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Topics |
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
- Carcinoma, Squamous Cell
(metabolism)
- Epidermal Cells
- Epidermis
(drug effects)
- Humans
- Hydroxyeicosatetraenoic Acids
(metabolism)
- Naphthols
(pharmacology)
- Receptors, Cell Surface
(antagonists & inhibitors)
- Receptors, Eicosanoid
- Skin Neoplasms
(metabolism)
- Tumor Cells, Cultured
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