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钾通道开放剂拮抗4-氨基吡啶诱发大鼠肥大细胞释放组胺

POTASSIUM CHANNEL OPENERS ANTAGONIZE4-AMINOPYRIDINE INDUCED HISTAMINE RELEASE FROM RAT PERITONEAL MAST CELLS

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【作者】 陈志刚徐建华

【Author】 ZGChen andJHXu(Department of Pharmacology ,Faculty of Pharmaceutical Sciences ,Zhejiang Medical University ,Hangzhou 310031)

【机构】 浙江医科大学药学系药理学教研室

【摘要】 4-氨基吡啶(4-AP)能诱发大鼠腹腔肥大细胞(PMC)释放组胺,且呈浓度依赖关系。钾通道开放剂二氮嗪(Dia),米诺地尔(Min)及钙拮抗剂硝苯啶(Nif)均能明显抑制4-AP诱发大鼠PMC释放组胺。实验结果提示,大鼠肥大细胞膜上可能存在钾通道,4-AP可能通过阻滞钾通道,使钙通道开放,Ca2+内流增加而促进组胺释放,钾通道开放剂可能是一类新的组胺释放拮抗剂。

【Abstract】 AMinopyridine (4-AP)was shown to promote histamine release from isolatedrat peritoneal mast cells(PMC )in a dose-dependent manner.Potassium channel openers ,minoxidil(Min)200 mg·kg-1 ig,diazoxide(Dia) 500 μmol·L-1 in vitro and calcium antagonist nifedipine(Nif)125 mg· kg-1 ig were found to inhibit 4-AP induced histamine release from rat PMC. Electronmicroscopy revealed that 4-AP caused partial degranulation of PMC and extrusion of granules and Min200 mg· kg-1 ig retarded this phenomenon. These results provide evidence that potassium channelsare present in rat mast cell membrane and indicate that the mechanism of histamine release by 4-APmay be related to its potassium channel blocking effect. As a result of this effect, the calcium channelsopen and Ca2+ influx to the mast cells increases,thus eliciting histamine release. Potassium channelopeners seemed to be a new group of inhibitors of histamine release from mast cells.

【基金】 国家自然科学基金
  • 【文献出处】 药学学报 ,ACTA PHARMACEUTICA SINICA , 编辑部邮箱 ,1995年10期
  • 【分类号】R965
  • 【被引频次】6
  • 【下载频次】43
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