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Role of glycoproteins having affinity to GlcNAc-oligomer specific DSA lectin, Putative receptor coupled to histamine release including Gi protein pathway of mast cells.

对 GlcNAc 寡聚物特异性 DSA 凝集素具有亲和力的糖蛋白的作用，与组胺释放偶联的推定受体，包括肥大细胞的 Gi 蛋白途径。

基本信息

批准号：
06672206
负责人：
SUZUKI Tamiko
金额：
$ 1.41万
依托单位：
Meiji College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Rat peritoneal mast cells have two activation pathway, an lgE-dependent pathway and an lgE-independent, pertussis toxin-sensitive G-protein (Gi) pathway. GlcNAc-oligomer specific lectin Datura stramonium agglutin (DSA) is one of the agonists of the lgE-independent action sites (putative recepotor) of the Gi-protein pathway. Their initial activation induced by DSA was a transient increase of intracellular calcium concentration followed by assembly of cytoskeleton as was compound 48/80 (48/80) by the method of confocal fluorescence microscopic analysis. Mast cell activation induced by DSA was sugar-specific and inhibited by other GlcNAc-specific lectins, such as WGA, STA and LEA, but not by ConA.Antagonist lectins bound to the corresponding glycoproteins and did not activate the Gi-protein pathway by themselves, but interfered with the interaction between the glycoproteins and DSA.The basic releasers 48/80, PE16 and bradykinin additively enhanced the histamine release induced by DSA, sug … More gesting that they share the same mechanisms of action, in which glycoproteins containing GlcNAc-residues were involved. Cationic benzalkonium chloride, an antagonist of Gi, irreversively inhibited the histamine release induced by DSA, but anionic polymer haparin did not. However, the histamine release induced by 48/80 or PE16 was inhibited by benzalkonium chloride and aniomic polymers (heparin, de-N-sulfated heparin, poly-aspartic acid, and poly-glutamic acid). Sialic acid was also important, since MAM (sialic acid-specific lectin) and neuraminidase inhibited the histamine release induced by DSA, 48/80, PE16, substance P and bradykinin. We stained the glycoproteins of rat peritoneal mast cells. At least four glycoproteins with affinity to DSA, WGA and MAM, and sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be putative receptors coupled to histamine release including the Gi-protein pathway. These studies may have important implications of the development of therapeutically useful inhibitors and antagonists. Less

大鼠腹腔肥大细胞有两条活化途径，一条依赖IgE的途径和一条不依赖IgE的百日咳毒素敏感性G蛋白（Gi）途径。洋金花凝集素（Datura stramonium agglutin，DSA）是Gi蛋白途径中的一种非IgE依赖性作用位点（推定的受体）的激动剂。共聚焦荧光显微镜分析显示，DSA诱导的细胞活化是细胞内钙离子浓度的瞬时升高，随后是细胞骨架的组装，如化合物48/80（48/80）。DSA诱导的肥大细胞活化是糖特异性的，其他GlcNAc特异性凝集素如WGA、STA和莱亚都能抑制，而ConA则不起作用。拮抗凝集素与相应的糖蛋白结合，本身不激活Gi蛋白通路，但干扰糖蛋白与DSA的相互作用。PE 16和缓激肽可加和地增强DSA诱导的组胺释放，suggesting ...更多信息推测它们具有相同的作用机制，其中涉及含有GlcNAc残基的糖蛋白。Gi拮抗剂苯扎氯铵可不可逆地抑制DSA诱导的组胺释放，而阴离子聚合物肝素则无此作用。然而，苯扎氯铵和阴离子聚合物（肝素、去N-硫酸化肝素、聚天冬氨酸和聚谷氨酸）可抑制48/80或PE 16诱导的组胺释放。唾液酸也很重要，因为MAM（唾液酸特异性凝集素）和神经氨酸酶抑制由DSA、48/80、PE 16、P物质和缓激肽诱导的组胺释放。我们对大鼠腹腔肥大细胞的糖蛋白进行了染色。凝集素印迹法检测到至少四种对DSA、WGA和MAM具有亲和力且对神经氨酸酶处理敏感的糖蛋白。它们中的一些可能是与组胺释放偶联的推定受体，包括Gi蛋白途径。这些研究可能对开发治疗上有用的抑制剂和拮抗剂具有重要意义。少