Perpiña M, de Diego A, Compte L, Bertó L, Cortijo J, Morcillo E J
Servicio de Neumología, Hospital Universitario La Fe, Valencia, Spain.
Fundam Clin Pharmacol. 1996;10(1):33-7. doi: 10.1111/j.1472-8206.1996.tb00147.x.
Tracheal strips from normal and actively sensitized guinea pigs were studied to determine the responses to serotonin (5-hydroxytryptamine, 5-HT; 1 nM-0.1 mM) and ouabain (0.1 microM-0.1 mM), and the effects of increasing the extracellular calcium (Cao) concentration on tonic contractions elicited by 5-HT. Sensitized trachea exhibited an increased responsiveness and sensitivity to 5-HT and ouabain. Increases in Cao to achieve final concentrations of 5, 10 and 20 mM caused concentration-related relaxations of normal and sensitized tissues contracted to a similar plateau level with 5-HT. Inhibition of the Na+/K(+)-ATPase by ouabain (10 microM) reversed the effects of Cao from relaxation to contraction in normal and sensitized tissues contracted with 5HT. Sensitized preparations showed reduced relaxations in response to Cao (10-20 mM), and sensitized, ouabain-treated, trachea showed augmented contractions to Cao (10-20 mM) when compared to normal tissues. These results demonstrate a decreased membrane-stabilizing effect of Cao in sensitized trachea and the implication of the Na+/K(+)-ATPase in the regulation of membrane stability by Cao, suggesting a possible relevance to those mechanisms underlying airway hyperreactivity.
研究了来自正常和主动致敏豚鼠的气管条,以确定其对血清素(5-羟色胺,5-HT;1 nM - 0.1 mM)和哇巴因(0.1 μM - 0.1 mM)的反应,以及增加细胞外钙(CaO)浓度对5-HT引起的张力性收缩的影响。致敏气管对5-HT和哇巴因的反应性和敏感性增加。将CaO增加至最终浓度5、10和20 mM会导致正常和致敏组织与5-HT收缩至相似平台水平时出现浓度相关的松弛。哇巴因(10 μM)抑制Na+/K(+)-ATP酶可使正常和与5-HT收缩的致敏组织中CaO的作用从松弛逆转至收缩。与正常组织相比,致敏制剂对CaO(10 - 20 mM)的反应松弛减少,致敏且经哇巴因处理的气管对CaO(10 - 20 mM)的收缩增强。这些结果表明,CaO在致敏气管中的膜稳定作用降低,且Na+/K(+)-ATP酶参与CaO对膜稳定性的调节,提示其可能与气道高反应性的潜在机制相关。