Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent
Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent
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DOI：
10.1016/s0014-2999(00)00147-3
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发表时间：
2000-04-07
影响因子：
5
通讯作者：
Furuhama, K
中科院分区：
文献类型：
--
作者：
Mori, K;Maru, C;Furuhama, K
本研究旨在阐明左氧氟沙星（一种氟喹诺酮类抗菌药物）引起大鼠腹腔肥大细胞组胺释放的机制。左氧氟沙星从300 μ g/ml开始诱导浓度依赖性组胺分泌，而无乳酸脱氢酶泄漏，释放在30 s内迅速完成。这种作用取决于温度、能量、pH和细胞内Ca 2+，类似于碱性化合物化合物48/80的作用。与钙离子载体A23187不同。通过用百日咳毒素或苯扎氯铵（一种G（i）亚型的G蛋白的选择性抑制剂）预处理来防止左氧氟沙星或化合物48/80引起的组胺分泌。此外，由左氧氟沙星或化合物48/80引起的组胺释放被神经氨酸酶引起的细胞表面上的唾液酸残基的水解所抑制。这些结果表明，左氧氟沙星发挥组胺释放的机制可能与百日咳毒素敏感的G蛋白的激活密切相关。(C)2000 Elsevier Science B. V.保留所有权利。
The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 mu g/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca2+, similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187. histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G(i) subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins. (C) 2000 Elsevier Science B.V. All rights reserved.