Kirkup A J, Edwards G, Green M E, Miller M, Walker S D, Weston A H
School of Biological Sciences, University of Manchester, UK.
Eur J Pharmacol. 1996 Dec 12;317(1):165-74. doi: 10.1016/s0014-2999(96)00713-3.
The effects of niflumic acid on whole-cell membrane currents and mechanical activity were examined in the rat portal vein. In freshly dispersed portal vein cells clamped at -60 mV in caesium (Cs+)-containing solutions, niflumic acid (1-100 microM) inhibited calcium (Ca2+)-activated chloride currents (IC1(Ca)) induced by caffeine (10 mM) and by noradrenaline (10 microM). In a potassium (K+)-containing solution and at a holding potential of - 10 mV, niflumic acid (10-100 microM) induced an outward K+ current (IK(ATP)) which was sensitive to glibenclamide (10-30 microM). At concentrations < 30 microM and at a holding potential of -2 mV, niflumic acid had no effect on the magnitude of the caffeine- or noradrenaline-stimulated current (IBK(Ca)) carried by the large conductance, Ca(2+)-sensitive K+ channel (BKCa). However, at a concentration of 100 microM, niflumic acid significantly inhibited IBK(Ca)) evoked by caffeine (10 mM) but not by NS1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3 H) benzimidazolone; 20 microM). In Cs(+)-containing solutions, niflumic acid (10-100 microM) did not inhibit voltage-sensitive Ca2+ currents. In intact portal veins, niflumic acid (1-300 microM) inhibited spontaneous mechanical activity, an action which was partially antagonised by glibenclamide (1-10 microM), and contractions produced by noradrenaline (10 microM), an effect which was glibenclamide-insensitive. It is concluded that inhibition of ICl(Ca) and stimulation of IK(ATP) both contribute to the mechano-inhibitory actions of niflumic acid in the rat portal vein.
在大鼠门静脉中研究了尼氟酸对全细胞膜电流和机械活性的影响。在含铯（Cs⁺）溶液中于-60 mV钳制的新鲜分离门静脉细胞中，尼氟酸（1 - 100 μM）抑制了由咖啡因（10 mM）和去甲肾上腺素（10 μM）诱导的钙（Ca²⁺）激活氯电流（ICl(Ca)）。在含钾（K⁺）溶液中且保持电位为-10 mV时，尼氟酸（10 - 100 μM）诱导出一种对格列本脲（10 - 30 μM）敏感的外向钾电流（IK(ATP)）。在浓度<30 μM且保持电位为-2 mV时，尼氟酸对由大电导、Ca²⁺敏感钾通道（BKCa）介导的咖啡因或去甲肾上腺素刺激电流（IBK(Ca)）的幅度无影响。然而，在浓度为100 μM时，尼氟酸显著抑制咖啡因（10 mM）诱发的IBK(Ca)，但不抑制NS1619（1-(2'-羟基-5'-三氟甲基苯基)-5-三氟甲基-2(3H)苯并咪唑酮；20 μM）诱发的IBK(Ca)。在含Cs⁺的溶液中，尼氟酸（10 - 100 μM）不抑制电压敏感性Ca²⁺电流。在完整的门静脉中，尼氟酸（1 - 300 μM）抑制自发机械活性，这一作用部分被格列本脲（1 - 10 μM）拮抗，并且抑制去甲肾上腺素（10 μM）产生的收缩，这一效应不受格列本脲影响。结论是，抑制ICl(Ca)和刺激IK(ATP)均有助于尼氟酸在大鼠门静脉中的机械抑制作用。
