caa a22 4500 465764037 CHVBK 20180323111908.0 cr unu---uuuuu 170327e19901201xx s 000 0 eng 10.1007/BF00916375 doi (NATIONALLICENCE)springer-10.1007/BF00916375 Inflammation of guinea pig dermis [Elektronische Daten] Effects of leukotriene B4 receptor antagonist, SC-41930 [D. Fretland, D. Widomski, J. Zemaitis, R. Walsh, S. Levin, S. Djuric, R. Shone, B. Tsai, T. Gaginella] Neutrophil (PMNL) infiltration is a prominent feature of human psoriasis. Psoriatic skin lesions contain abnormally high amounts of leukotriene B4 (LTB4), itself a potent PMNL chemoattractant both in vivo and in vitro. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-propyl-2H-1-benzo-pyran-2-carboxylic acid}, an orally active LTB4 receptor antagonist, was tested topically in models of skin inflammation induced by 200 nmol of the calcium ionophore A23187 or 200μg phorbol-12-myristate-13-acetate (PMA) applied topically to the guinea pig ear as assessed by ear weight, levels of the PMNL marker enzyme myeloperoxidase (MPO), and histological examination (PMA model) at 4 and 18 h respectively. When coapplied topically with A23187 or PMA, SC-41930 significantly inhibited epidermal inflammation with ED50 values of 0.6 and 4 mg, respectively. SC-41930 treatment also was associated with lowered dermal LTB4 levels in both models. The PMA-induced skin inflammation model also was assessed histologically and revealed acanthosis, edema, PMNL infiltration, and rete ridge prominence as long as 96 h after a single application that was completely inhibited by SC-41930 topical coapplication. Furthermore, oral treatment (40 mg/kg) significantly reduced edema and inflammatory cell infiltration in both models. These models possess many of the characteristics of human psoriasis, and agents such as SC-41930 that demonstrate activity in these models may well have therapeutic utility in the treatment of human psoriasis. Plenum Publishing Corporation, 1990 Fretland D. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Widomski D. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Zemaitis J. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Walsh R. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Levin S. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Djuric S. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Shone R. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Tsai B. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Gaginella T. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut Inflammation Kluwer Academic Publishers-Plenum Publishers 14/6(1990-12-01), 727-739 0360-3997 14:6<727 1990 14 10753 https://doi.org/10.1007/BF00916375 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00916375 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fretland D. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Widomski D. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Zemaitis J. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Walsh R. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Levin S. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Djuric S. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Shone R. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Tsai B. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 700 1- Gaginella T. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois aut NATIONALLICENCE 773 0- Inflammation Kluwer Academic Publishers-Plenum Publishers 14/6(1990-12-01), 727-739 0360-3997 14:6<727 1990 14 10753 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer