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

P. Arenberger, A. Raap, B. Armah, L. Kemény, T. Ruzicka

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 K(i) 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 (B(max) of 215,000 ± 21,000 receptors per cell) or on receptor affinity (K(d) 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.

Original languageEnglish
Pages (from-to)148-151
Number of pages4
JournalSkin Pharmacology
Volume6
Issue number2
Publication statusPublished - 1993

Fingerprint

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Lipoxygenase Inhibitors
Lipoxygenase
Cell Line
Skin Diseases
Arachidonate 5-Lipoxygenase
Pharmaceutical Preparations
12-hydroxyeicosatetraenoic acid receptor
2-(phenylmethyl)-1-naphthol
Anti-Inflammatory Agents
Binding Sites
Inflammation
Skin

Keywords

  • 12-HETE binding
  • DuP 654
  • Keratinocyte

ASJC Scopus subject areas

  • Dermatology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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. / Arenberger, P.; Raap, A.; Armah, B.; Kemény, L.; Ruzicka, T.

In: Skin Pharmacology, Vol. 6, No. 2, 1993, p. 148-151.

Research output: Contribution to journalArticle

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