Eleno N, Botana L, Espinosa J
Department of Physiology and Pharmacology, University of Salamanca, Spain.
Int Arch Allergy Appl Immunol. 1990;92(2):162-7. doi: 10.1159/000235208.
Histamine secretion and 45Ca uptake processes were studied in mast cells treated with four K+ channel blocking drugs in physiological saline and in media containing different ionic concentrations. Quinine, 4-aminopyridine and sparteine were effective as histamine-releasing agents when mast cells were incubated in physiologic saline solution. The dose-response profile obtained was in the range of 0.1-0.5 mM for quinine, 1-10 for 4-aminopyridine and 0.5-5 mM for sparteine and did not show significant differences between purified and unpurified mast cells. By contrast, tetraethylammonium (1-100 mM) did not induce histamine release. The presence of high K+ or Rb+ concentrations in the medium (Tris-K+ or Tris-Rb+, both at 150 mM) displaced the profile obtained to the right in cells stimulated with 4-aminopyridine or sparteine, but abolished histamine release induced by quinine. Additionally, all three K+ channel blockers increased 45Ca uptake in mast cells. The exact mechanism of the action of K+ channel blockers on mast cells is unknown. However, the fact that the drugs used were effective as histamine-releasing and 45Ca uptake promoters suggests both that mast cells might be endowed with a K+ channel activity and that the blockade of this should open certain calcium channels, leading to elevated intracellular Ca2+ levels which in turn activate mast cell secretion.
在含有不同离子浓度的生理盐水和培养基中，用四种钾通道阻断药物处理肥大细胞，研究组胺分泌和45Ca摄取过程。当肥大细胞在生理盐溶液中孵育时，奎宁、4-氨基吡啶和鹰爪豆碱作为组胺释放剂有效。获得的剂量反应曲线范围为：奎宁0.1 - 0.5 mM，4-氨基吡啶1 - 10 mM，鹰爪豆碱0.5 - 5 mM，纯化和未纯化的肥大细胞之间未显示出显著差异。相比之下，四乙铵（1 - 100 mM）未诱导组胺释放。培养基中高浓度的K+或Rb+（Tris-K+或Tris-Rb+，均为150 mM）使在用4-氨基吡啶或鹰爪豆碱刺激的细胞中获得的曲线向右移动，但消除了奎宁诱导的组胺释放。此外，所有三种钾通道阻滞剂均增加了肥大细胞对45Ca的摄取。钾通道阻滞剂对肥大细胞的具体作用机制尚不清楚。然而，所用药物作为组胺释放剂和45Ca摄取促进剂有效的事实表明，肥大细胞可能具有钾通道活性，并且对该通道的阻断应会打开某些钙通道，导致细胞内Ca2+水平升高，进而激活肥大细胞分泌。
