THE LIPOXYGENASE INHIBITOR 2-PHENYLMETHYL-1-NAPHTHOL (DUP-654) IS A 12(S)-HYDROXYEICOSA-TETRAENOIC ACID RECEPTOR ANTAGONIST IN THE HUMAN EPIDERMAL-CELL LINE SCL-II

The lipoxygenase inhibitor 2-phenylmethyl-1-naphthol (DuP 6 5 4) has b een shown to be an active anti-inflammatory drug in a murine skin infl ammation model. Since 12-HETE is assumed to have a pathophysiological role in inflammatory skin diseases, and epidermal cells possess high a ffinity 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 inhibito ry effect at concentrations between 10(-10) and 10(-5) M on specific 1 2(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 tha t DuP 654, in addition to its 5-lipoxygenase inhibitory activity, exhi bits 12-HETE receptor antagonist effect, and therefore may be of benef it in skin diseases with elevated 12-HETE levels.