Elsevier

Biochemical Pharmacology

Volume 36, Issue 9, 1 May 1987, Pages 1461-1466
Biochemical Pharmacology

Experiments on the mode of action of piriprost (U-60,257), an inhibitor of leukotriene formation in cloned mouse mast cells and in rat basophil leukemia cells

https://doi.org/10.1016/0006-2952(87)90111-0Get rights and content

Abstract

We studied the effect of piriprost, an inhibitor of sulfidopeptide leukotriene (LT) formation, on the generation of the known products of the 5-lipoxygenase pathway of arachidonate metabolism in calcium ionophore A23187-challenged rat basophil leukemia cells and cloned, growth factor-dependent, mouse mast cells. Piriprost inhibited the formation of 5-hydroxyeicosatetraenoic acid (5-HETE), and LTB4, and the sulfidopeptide leukotrienes (LTC4 in the mouse mast cells and both LTC4 and a mixture of LTD4 and LTE4 in the rat basophil leukemia cells) in parallel (IC50 values ranged between 9 and 14 μM for the mouse mast cells and between 15 and 50 μM for the basophil leukemia cells). Our previous observation that piriprost is only a very weak inhibitor of the solubilized LTC synthase of rat basophil leukemia cells was extended to similar enzyme preparations derived from the mouse mast cells (IC50 1.5 mM). The results are consistent with the conclusion that piriprost acts as an inhibitor of the 5-lipoxygenase reaction and that its activity in intact cells is not likely to involve the inhibition of the LTC synthase.

References (27)

  • R.P. Orange et al.

    Adv. Immun.

    (1969)
  • M.C. Holroyde et al.

    Lancet

    (1981)
  • M.K. Bach

    Biochem. Pharmac.

    (1984)
  • R.J. Smith et al.

    Biochem. biophys. Res. Commun.

    (1982)
  • F.F. Sun et al.

    Prostaglandins

    (1983)
  • O. Cromwell et al.

    Prostaglandins

    (1984)
  • M.K. Bach et al.

    Archs Biochem. Biophys.

    (1984)
  • M.K. Bach et al.

    Biochem. Pharmac.

    (1986)
  • M.K. Bach et al.

    J. Allergy clin. Immun.

    (1984)
  • R.N. Young et al.

    Prostaglandins

    (1982)
  • S-E. Dahlén et al.
  • A.G. Leiten et al.
  • P. Hedqvist et al.

    Adv. Prosiaglandin, Thromboxane, Leukotriene Res.

    (1983)
  • Cited by (13)

    • 1,4-Dihydronaphthoquinones as water-soluble inhibitors of 5-lipoxygenase

      1990, Prostaglandins, Leukotrienes and Essential Fatty Acids
    View all citing articles on Scopus
    View full text