Dithranol-induced down-regulation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptors in a human epidermal cell line.
The effects of dithranol and its therapeutically inactive oxidation product, danthrone, on 12(S)-HETE binding to the human epidermal cell line SCL-II were studied. Dithranol (0.25-1 microgram/ml), in contrast to danthrone, induced a substantial decrease in 12(S)-HETE binding in a dose-dependent manner. The inhibition occurred after a latency period of 6 h, reached its maximum at 18-24 h and slowly declined thereafter. At a concentration of 1 microgram/ml, the drug led to an approximately 50% decrease in the number of specific high-affinity 12(S)-HEFE receptors (Bmax), whereas receptor affinity (Kd) showed no change. The down-regulation of 12(S)-HETE receptors on epidermal cells by dithranol may contribute to its antipsoriatic action.
Kemény
L
L
Department of Dermatology, University of Munich, Federal Republic of Germany.
Gross
E
E
Arenberger
P
P
Ruzicka
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000875:Anthralin / Q000494:pharmacology* / Q000627:therapeutic use; D000880:Anthraquinones / Q000494:pharmacology; D002460:Cell Line; D015536:Down-Regulation; D004817:Epidermis / Q000737:chemistry*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D018055:Receptors, Eicosanoid
C066652:12-hydroxyeicosatetraenoic acid receptor; D000880:Anthraquinones; D006893:Hydroxyeicosatetraenoic Acids; D011956:Receptors, Cell Surface; D018055:Receptors, Eicosanoid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000875:Anthralin; C004315:danthron