[Potassium channel openers antagonize 4-aminopyridine induced histamine release from rat peritoneal mast cells].
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.
Chen
Z G
ZG
Department of Pharmacology, Zhejiang Medical University, Hangzhon.
Xu
J H
JH
D015761:4-Aminopyridine / Q000037:antagonists & inhibitors*; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008914:Minoxidil / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D008914:Minoxidil; D015761:4-Aminopyridine; D003981:Diazoxide