Chen Z G, Xu J H
Department of Pharmacology, Zhejiang Medical University, Hangzhon.
Yao Xue Xue Bao. 1995;30(10):736-40.
4-Aminopyridine (4-AP) was shown to promote histamine release from isolated rat peritoneal mast cells (PMC) in a dose-dependent manner. Potassium channel openers, minoxidil (Min) 200 mg.kg-1 ig, diazoxide (Dia) 500 mumol.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. Electron microscopy revealed that 4-AP caused partial degranulation of PMC and extrusion of granules and Min 200 mg.kg-1 ig retarded this phenomenon. These results provide evidence that potassium channels are present in rat mast cell membrane and indicate that the mechanism of histamine release by 4-AP may be related to its potassium channel blocking effect. As a result of this effect, the calcium channels open and Ca2+ influx to the mast cells increases, thus eliciting histamine release. Potassium channel openers seemed to be a new group of inhibitors of histamine release from mast cells.
4-氨基吡啶（4-AP）已被证明能以剂量依赖的方式促进从分离的大鼠腹膜肥大细胞（PMC）中释放组胺。发现钾通道开放剂，如200mg.kg-1灌胃给予米诺地尔（Min）、500μmol.L-1体外给予二氮嗪（Dia）以及125mg.kg-1灌胃给予钙拮抗剂硝苯地平（Nif），均可抑制4-AP诱导的大鼠PMC组胺释放。电子显微镜显示，4-AP导致PMC部分脱颗粒和颗粒挤出，而200mg.kg-1灌胃给予的Min可延缓此现象。这些结果证明大鼠肥大细胞膜上存在钾通道，并表明4-AP释放组胺的机制可能与其钾通道阻断作用有关。由于这种作用，钙通道开放，肥大细胞内Ca2+内流增加，从而引发组胺释放。钾通道开放剂似乎是一类新的肥大细胞组胺释放抑制剂。
