SC-41930, a leukotriene B4 receptor antagonist, inhibits 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) binding to epidermal cells.
SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxyl]-3, 4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, a potent leukotriene-B4 (LTB4) receptor antagonist, inhibits in vivo 12-hydroxyeicosatetraenoic acid (12-HETE)-induced neutrophil infiltration, suggesting a potential 12-HETE receptor antagonist effect, as well. 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 SC-41930 on 12(S)-HETE binding to the human epidermal cell line, SCL-II. SC-41930 antagonized the 12(S)-HETE binding to SCL-II cells with a Ki of 480 nM. This Ki value is similar to that obtained for the inhibition of LTB4 binding to human neutrophils. Our results show that SC-41930, in addition to its LTB4 receptor antagonist effect, exhibits 12-HETE receptor antagonist effect as well, and therefore may be of benefit in skin diseases with elevated 12-HETE levels.
Kemény
L
L
Department of Dermatology, University of Munich, FRG.
Ruzicka
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001578:Benzopyrans / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D018102:Receptors, Leukotriene B4; D014407:Tumor Cells, Cultured
D001578:Benzopyrans; D006893:Hydroxyeicosatetraenoic Acids; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; C059950:SC 41930; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid