Inhibition of Radiolabeled Leukotriene-Binding by AS-35 in Guinea Pig Lung Membrane Fraction.
スポンサーリンク
概要
- 論文の詳細を見る
The inhibitory 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 peptide leukotriene (LT) antagonist, on specific bindings of radiolabeled LTC<SUB>4</SUB> and LTD<SUB>4</SUB> in guinea pig lung membrane were investigated to clarify the mechanism by which this agent inhibited LT-induced physiological responses. Binding assays were performed at 20°C in 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM CaCl</SUB>2</SUB>, 10 MM MgCl<SUB>2</SUB> and 10 mM cysteine in the absence (LTD<SUB>4</SUB> binding assay) or presence (LTC<SUB>4</SUB> binding assay) of 80 mM L-serine borate. Scatchard analysis of each LT specific binding indicated a single and high affinity binding site with a K<SUB>d</SUB> of 0.21 ± 0.05 nM and B<SUB>max</SUB> of 808 ± 71 fmol/mg protein for [<SUP>3</SUP>H]-LTD<SUB>4</SUB>, and with a K<SUB>d</SUB> of 21.6 ± 3.8 nM and B<SUB>max</SUB> of 74.9 ± 2.6 pmol/mg protein for [<SUP>3</SUP>H]-LTC<SUB>4</SUB>. Competition binding studies showed that AS-35 antagonized [<SUP>3</SUP>H]-LTD<SUB>4</SUB> specific binding with a K<SUB>i</SUB> value of 92.7 nM. In contrast, AS-35 was 100 times less effective in inhibiting [<SUP>3</SUP>H]-LTC<SUB>4</SUB> specific binding, compared with [<SUP>3</SUP>H]-LTD<SUB>4</SUB> specific binding. These results indicate that AS-35 interacts directly with peptide LTs receptors, especially the LTD<SUB>4</SUB> specific binding site to produce its pharmacological effects.
- 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.
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.