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The effect of leukotriene-B4 receptor antagonist, SC-41930, on acetic acid-induced colonic inflammation. 1989

D J Fretland, and S Levin, and B S Tsai, and S W Djurić, and D L Widomski, and J M Zemaitis, and R L Shone, and R F Bauer
Department of Gastrointestinal Diseases Research, G. D. Searle and Co., Skokie, IL 60077.

SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-p ropyl- 2H-1-benzopyran-2-carboxylic acid, is a potent in vitro leukotriene-B4 (LTB4) receptor antagonist. LTB4 levels are elevated in colonic tissue of inflammatory bowel disease (IBD) patients which may account for the high degree of neutrophil (PMN) infiltration. The guinea pig acetic acid-induced colonic inflammation model has characteristics of IBD including PMN infiltration, edema, ulceration and necrosis. The model was used to evaluate the effect of SC-41930. SC-41930 was given orally, 30 min before and after intrarectal administration of 3% acetic acid. The PMN marker enzyme, myeloperoxidase, was measured along with histological evaluation to assess inflammation. Both parameters showed significantly less inflammation in SC-41930 treated animals with an oral ED50 of 20 mg/kg. These study results with an LTB4 receptor antagonist indicate a role for LTB4 in colonic inflammation and that an LTB4 receptor antagonist may be beneficial for treatment of IBD.

UI MeSH Term Description Entries
D008297 Male Males
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D003092 Colitis Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER. Colitides
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000085 Acetates Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure. Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001578 Benzopyrans Compounds with a core of fused benzo-pyran rings. Benzopyran,Chromene,Chromenes
D018102 Receptors, Leukotriene B4 A class of cell surface leukotriene receptors with a preference for leukotriene B4. Leukotriene B4 receptor activation influences chemotaxis, chemokinesis, adherence, enzyme release, oxidative bursts, and degranulation in polymorphonuclear leukocytes. There are at least two subtypes of these receptors. Some actions are mediated through the inositol phosphate and diacylglycerol second messenger systems. LTB4 Receptors,Leukotriene B4 Receptors,LTB4 Receptor,Leukotriene B4 Receptor,Receptor, LTB4,Receptor, Leukotriene B4,Receptors, LTB4

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