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Effect of a leukotriene B4 receptor antagonist on leukotriene B4-induced neutrophil chemotaxis in cavine dermis

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Abstract

Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated as a mediator in a number of inflammatory diseases. When injected intradermally into the cavine, LTB4 elicits a dose-dependent immigration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8-propyl-2H-l-benzopyran-2-carboxylic acid, a potent LTB4 receptor antagonist inhibited the chemotactic actions of LTB4 when coadministered into the dermal site and when given intravenously or orally with ED50 values of 200 ng, 0.5 mg/kg, and 0.6 mg/ kg respectively. This compound may well have application in disease states, such as inflammatory bowel disease and psoriasis, where LTB4 is implicated as a proinflammatory mediator.

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Authors and Affiliations

  1. Department of Gastrointestinal Research, G. D. Searle and Co., 4901 Searle Parkway, 60077, Skokie, Illinois

    D. J. Fretland, D. L. Widomski, J. M. Zemaitis, S. W. Djurić & R. L. Shone

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  1. D. J. Fretland
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  2. D. L. Widomski
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  3. J. M. Zemaitis
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  4. S. W. Djurić
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  5. R. L. Shone
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Fretland, D.J., Widomski, D.L., Zemaitis, J.M. et al. Effect of a leukotriene B4 receptor antagonist on leukotriene B4-induced neutrophil chemotaxis in cavine dermis. Inflammation 13, 601–605 (1989). https://doi.org/10.1007/BF00916766

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