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[豚鼠食管黏膜肌层体外过敏反应性收缩的药理学特征]

[Pharmacological characterizations of the in vitro anaphylactic contraction of the guinea-pig esophageal muscularis mucosae].

作者信息

Fujinuma S

机构信息

Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1988 Jan;91(1):17-27. doi: 10.1254/fpj.91.17.

Abstract

Characteristics of the antigen-induced contraction of the isolated esophageal muscularis mucosae of actively sensitized guinea-pigs to ovalbumin (OA) were examined in vitro, and they were compared with those of compound 48/80- or polymyxin B-induced contraction. OA, above 0.01 microgram/ml, produced a sustained contraction of the sensitized esophageal muscularis mucosae, the amplitude of which was about 80-100% of the maximum contraction induced by carbachol (10 microM), while compound 48/80 and polymyxin B (10-300 micrograms/ml) produced less potent contractions of the non-sensitized esophageal muscularis mucosae. Contractions to OA or compound 48/80, but not to polymyxin B, were diminished by their repetitive applications. The contractile responses to OA, compound 48/80 and polymyxin B depended on the external calcium concentrations, and were abolished in the calcium-free medium. Pretreatment with tetrodotoxin (0.3 microM), atropine (0.3 microM), diphenhydramine (30 microM) or DSCG (300 microM) did not modify any of these contractions, whereas BW755C (100 microM) and quercetin (10 microM) significantly inhibited them. Indomethacin (10 microM) largely prevented only the polymyxin B-induced contraction, while FPL55712 (10 microM) inhibited both contractions to OA and compound 48/80. These findings indicate that the OA-induced anaphylactic contraction of the esophageal muscularis mucosae taken from the OA-sensitized guinea-pig may be an indirect action via the stimulation of releases of some mast cell-derived spasmogens. The spasmogens may involve the lipoxygenase products of arachidonic acid in part, but not histamine, acetylcholine or the cyclooxygenase products.

摘要

在体外研究了主动致敏豚鼠分离的食管肌层黏膜对卵清蛋白(OA)抗原诱导收缩的特性,并将其与化合物48/80或多粘菌素B诱导的收缩特性进行比较。浓度高于0.01微克/毫升的OA可使致敏的食管肌层黏膜产生持续收缩,其幅度约为卡巴胆碱(10微摩尔)诱导的最大收缩幅度的80 - 100%,而化合物48/80和多粘菌素B(10 - 300微克/毫升)对未致敏的食管肌层黏膜产生的收缩作用较弱。OA或化合物48/80重复给药后收缩减弱,但多粘菌素B重复给药后收缩无变化。对OA、化合物48/80和多粘菌素B的收缩反应依赖于细胞外钙浓度,在无钙培养基中收缩反应消失。用河豚毒素(0.3微摩尔)、阿托品(0.3微摩尔)、苯海拉明(30微摩尔)或色甘酸钠(300微摩尔)预处理均不改变这些收缩反应,而BW755C(100微摩尔)和槲皮素(10微摩尔)可显著抑制这些收缩反应。吲哚美辛(10微摩尔)仅在很大程度上阻止多粘菌素B诱导的收缩,而FPL55712(10微摩尔)可抑制对OA和化合物48/80的收缩反应。这些结果表明,从OA致敏豚鼠获取的食管肌层黏膜的OA诱导过敏收缩可能是通过刺激某些肥大细胞衍生的致痉物质释放而产生的间接作用。这些致痉物质可能部分涉及花生四烯酸的脂氧合酶产物,但不涉及组胺、乙酰胆碱或环氧化酶产物。

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