SC-41930: An inhibitor of leukotriene B4-stimulated human neutrophil functions
- G.D. Searle Co., Skokie, IL (USA)
SC-41930 was evaluated for effects on human neutrophil chemotaxis and degranulation. At concentrations up to 100 microM, SC-41930 alone exhibited no effect on neutrophil migration, but dose-dependently inhibited neutrophil chemotaxis induced by leukotriene B4 (LTB4) in a modified Boyden chamber. Concentrations of SC-41930 from 0.3 microM to 3 microM competitively inhibited LTB4-induced chemotaxis with a pA2 value of 6.35. While inactive at 10 microM against C5a-induced chemotaxis, SC-41930 inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis, with 10 times less potency than against LTB4-induced chemotaxis. SC-41930 inhibited (3H)LTB4 and (3H)fMLP binding to their receptor sites on human neutrophils with KD values of 0.2 microM and 2 microM, respectively. SC-41930 also inhibited neutrophil chemotaxis induced by 20-OH LTB or 12(R)-HETE. At concentrations up to 10 microM, SC-41930 alone did not cause neutrophil degranulation, but inhibited LTB4-induced degranulation in a noncompetitive manner. SC-41930 also inhibited fMLP- or C5a-induced degranulation, but was about 8 and 10 times less effective for fMLP and C5a, respectively. The results indicate that SC-41930 is a human neutrophil LTB4 receptor antagonist with greater specificity for LTB4 than for fMLP or C5a receptors.
- OSTI ID:
- 6897028
- Journal Information:
- Prostaglandins; (USA), Journal Name: Prostaglandins; (USA) Vol. 38:6; ISSN 0090-6980; ISSN PRGLB
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
COMPLEMENT
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
FUNCTIONS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LEUKOCYTES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
NEUTROPHILS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES