Nayler R A, Sparrow M P
Br J Pharmacol. 1983 Sep;80(1):163-72. doi: 10.1111/j.1476-5381.1983.tb11062.x.
The characteristics of vanadate-induced contraction of airways smooth muscle are described in isolated preparations of guinea-pig central and peripheral airways. Vanadate (1-1000 microM) induced sustained contractions of trachea and lung parenchymal strips within 1 min of challenge. It was more potent (P less than 0.001) on the lung strip (EC50 = 63 microM) than on the trachea (EC50 = 123 microM). The lung strip also developed greater maximum isometric tension (P less than 0.001) than the trachea. The efficacy on the lung strip was 2 and the trachea 0.6, relative to the response to acetylcholine (efficacy = 1). Vanadate-induced contractions of the trachea were not inhibited by atropine, mepyramine, phentolamine or indomethacin, nor after mast cell depletion by compound 48/80, showing that contractions were not mediated via specific receptors or by release of endogenous mediators of tone. Inorganic phosphate specifically inhibited vanadate responses in a dose-dependent and reversible manner, suggesting a common site of action. Contractions could be elicited in depolarized muscle and after treatment with ouabain plus propranolol, showing that membrane depolarization and inhibition of the Na, K-ATPase system were not involved in the contractile action of vanadate. Pretreatment of tracheal smooth muscle with verapamil had no influence on contractions elicited by vanadate. After removal of extracellular calcium, vanadate-induced contractions declined slowly with time, indicating that influx of extracellular calcium was not giving rise to contractions elicited by vanadate. Vanadate markedly increased the rate of calcium efflux from trachealis muscle loaded with 45Ca into both Ca2+-free and normal Krebs solutions; this is compatible with vanadate mobilizing an intracellular store of Ca2+. Such a store involving sites with Ca-ATPase activity would be consistent with the action of vanadate in isolated membrane preparations. Membrane-skinned tracheal fibres contracted by micromolar Ca2+ were relaxed by vanadate in a reversible dose-related manner, indicating that the contractile action of vanadate was not related to its interaction with proteins at the cross-bridge level.
在豚鼠中央和外周气道的离体标本中描述了钒酸盐诱导的气道平滑肌收缩的特征。钒酸盐（1 - 1000微摩尔）在刺激后1分钟内可诱导气管和肺实质条带产生持续收缩。它对肺条带的作用更强（P < 0.001）（半数有效浓度[EC50] = 63微摩尔），而对气管的作用较弱（EC50 = 123微摩尔）。肺条带产生的最大等长张力也比气管更大（P < 0.001）。相对于乙酰胆碱的反应（效能 = 1），对肺条带的效能为2，对气管的效能为0.6。钒酸盐诱导的气管收缩不受阿托品、美吡拉敏、酚妥拉明或吲哚美辛的抑制，在用48/80化合物使肥大细胞耗竭后也不受抑制，这表明收缩不是通过特定受体介导，也不是由内源性张力介质的释放介导。无机磷酸盐以剂量依赖性和可逆的方式特异性抑制钒酸盐反应，提示存在共同的作用位点。在去极化肌肉以及用哇巴因加普萘洛尔处理后仍可引发收缩，这表明膜去极化和钠钾 - ATP酶系统的抑制与钒酸盐的收缩作用无关。用维拉帕米预处理气管平滑肌对钒酸盐引发的收缩没有影响。去除细胞外钙后，钒酸盐诱导的收缩随时间缓慢下降，表明细胞外钙内流并非钒酸盐引发收缩的原因。钒酸盐显著增加了加载有45Ca的气管肌中钙向无钙和正常 Krebs 溶液的外流速率；这与钒酸盐动员细胞内钙库一致。这样一个涉及具有钙 - ATP酶活性位点且与钒酸盐在离体膜制剂中的作用相符的钙库。微摩尔浓度的Ca2+使去膜的气管纤维收缩，而钒酸盐以可逆的剂量相关方式使其松弛，这表明钒酸盐的收缩作用与其在横桥水平与蛋白质的相互作用无关。
