钾通道开放剂的抗过敏作用及其机制

用多种抗变态反应实验方法,研究钾通道开放剂米诺地尔(Min)与二氮嗪(Dia)的抗过敏作用,并探讨其作用机制。结果表明,Min能抑制大鼠同种被动皮肤过敏反应,拮抗5-HT引起的大鼠皮肤血管通透性增高。Dia和Min均能抑制豚鼠离体回肠平滑肌的过敏性收缩,Dia并能抑制A₂₃₁₈₇和化合物48/80诱发的肥大细胞释放组胺。因此钾通道开放剂Min与Dia具有抗过敏作用,作用的主要机理是抑制肥大细胞外Ca²⁺内流和细胞内贮存钙的释放,从而抑制组胺的释放,此可能与药物开放钾通道的作用有关。

The anti-anaphylactic action of potassium channel openers and its mechanism]

The anti-anaphylactic action of potassium channel openers was studied and reported in this paper. Minoxidil(Min) was shown to inhibit passive cutaneous anaphylaxis in rats. Diazoxide (Dia) and Min were found to inhibit antigen-induced guinea-pig ileum smooth muscle contraction in vitro. Min was shown to antagonize 5-HT-induced capillary permeability in rat skin. Dia was demonstrated to inhibit histamine release from rat peritoneal mast cells induced by A23187 and compound 48/80, but it failed to antagonize guinea-pig ileum smooth muscle contraction induced by histamine in vitro. These results provide evidence that potassium channel openers may be a new group of inhibitors of histamine release and indicate that the mechanism of its anti-anaphylactic action may be related to its potassium channel opening effect. As a result of this effect, Ca2+ influx to the mast cells decreases and Ca2+ release from calcium storage was inhibited, thus inhibiting histamine release.