Peptide Leukotriene Antagonistic Activity of AS-35, a New Antiallergic Drug.
スポンサーリンク
概要
- 論文の詳細を見る
-The effects of 9-[(4-acetyl-3-hydroxy-2-<I>n</I>-propylphenoxy)methyl]-3-(1<I>H</I>-tetrazol-5-yl)-4<I>H</I>-pyrido[1, 2-<I>a</I>]pyrimidin-4-one (AS-35), a newly synthesized compound, on leukotrienes (LTs) antagonistic activities were investigated in vitro and in vivo. In isolated guinea pig preparations, AS-35 antagonized LTC<SUB>4</SUB>-, LTD<SUB>4</SUB>- and LTE<SUB>4</SUB>-induced contractions of the ileum with IC<SUB>50</SUB> values of 8 nM, 4 nM and 3 nM, respectively. In the trachea, the agent also antagonized LTD<SUB>4</SUB>- and LTE<SUB>4</SUB>-induced contractions with IC<SUB>50</SUB> values of 10 nM and 20 nM, respectively. However, LTC<SUB>4</SUB>-induced tracheal contraction in the presence of L-serine borate was not antagonized by AS-35. Histamine-, acetylcholine-, serotonin- and bradykinin-induced contractions of the ileum, carbachol-, prostaglandin D<SUB>2</SUB>-, prostaglandin F<SUB>2α</SUB>-induced contractions of the trachea and LTE<SUB>4</SUB>-induced chemotaxis of rat polymorphonuclear leukocytes were not inhibited by AS-35. As to the in vivo models, AS-35 (i.v.) dose-dependently antagonized bronchoconstriction induced by i.v.-injection of LTC<SUB>4</SUB> and LTD<SUB>4</SUB> in anesthetized guinea pigs, but did not inhibit histamine-induced bronchoconstriction. Oral administration of AS-35 also antagonized LTD<SUB>4</SUB>- as well as antigen-induced LT-mediated bronchoconstriction. In addition, LTD<SUB>4</SUB>-induced increase in the cutaneous vascular permeability of guinea pig was inhibited by the drug (p.o.). These results indicate that AS-35 is an orally effective, potent and selective peptide LT antagonist.
- 公益社団法人 日本薬理学会の論文
著者
-
Yanagihara Yukiyoshi
Clinical Research Center For Allergy And Rheumatology National Hospital Organization Sagamihara Nati
-
Kasai Hiroshi
Product Development Laboratories, Tokyo Tanabe Co., Ltd.
-
YANAGIHARA Yukiyoshi
Clinical Research Center for Allergy, National Sagamihara Hospital
-
Kawashima Toshio
Product Development Laboratories, Tokyo Tanabe Co., Ltd.
-
Omura Shigeki
Product Development Laboratories, Tokyo Tanabe Co., Ltd.
関連論文
- Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells
- Induction of IgE synthesis by genetically modified CD8+ T cells of a patient with adenosine deaminase deficiency
- Differential regulation of thymus- and activation-regulated chemokine induced by IL-4, IL-13, TNF-α and IFN-γ in human keratinocyte and fibroblast
- Blocking the CD154-CD40 interaction with anti-CD154 antibody differntially regulates interleukin-4 synthesis in T cells and IgE production in B cells
- Molecular regulation of human IgE synthesis
- Recombinant soluble form of the high-affinity IgE receptor α subunit and anti-IgE antibody inhibit IgE synthesis by IgE-expressing B cells through distinct pathways
- Expression and Function of the Inducible Costimulator Ligand B7-H2 in Human Airway Smooth Muscle Cells
- Immunopharmacological studies on TBX, a new antiallergic drug. (4). Effects on type II to IV allergic reactions and immunological functions in animal models.
- Immunopharmacological studies on TBX, a new antiallergic drug. (2) inhibitory effects on histamine release from peritoneal mast cells and lung fragments of rats.
- Inhibition of Radiolabeled Leukotriene-Binding by AS-35 in Guinea Pig Lung Membrane Fraction.
- Suppression of IgE Production by IPD-1151T (Suplatast Tosilate), a New Dimethylsulfonium Agent: (2). Regulation of Human IgE Response.
- Suppression of IgE Production by IPD-1151T (Suplatast Tosilate), a New Dimethylsulfonium Agent: (1). Regulation of Murine IgE Response.
- Immunopharmacological studies on TBX, a new antiallergic drug. (1). Inhibitory effects on passive cutaneous anaphylaxis in rats and guinea pigs.
- Immunopharmacological studies on TBX, a new antiallergic drug. (3). Inhibitory effects on histamine release from lung fragments and bronchoconstriction in guinea pigs.
- Peptide Leukotriene Antagonistic Activity of AS-35, a New Antiallergic Drug.
- Effect of butyl 3-(1H-tetrazol-5-yl) oxanilate(MTB) on immunological or non-immunological histamine and SRS(-A) release from guinea-pig, monkey and human lung tissue.