SC-41930, a leukotriene B4 receptor antagonist, inhibits 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) binding to epidermal cells

Agents Actions. 1991 Mar;32(3-4):339-42. doi: 10.1007/BF01980895.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Benzopyrans / pharmacology*
  • Carcinoma, Squamous Cell
  • Epidermis / drug effects
  • Epidermis / metabolism*
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Leukotriene B4 / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Leukotriene B4
  • Tumor Cells, Cultured

Substances

  • Benzopyrans
  • Hydroxyeicosatetraenoic Acids
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • SC 41930
  • Leukotriene B4
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid