Stoner L C, Trimble M E
J Pharmacol Exp Ther. 1982 Jun;221(3):715-20.
The effects of the diuretic agents, MK-196 (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy acetic acid) and furosemide on function of medullary thick ascending limb (tALH) isolated from the rat kidney were studied. tALH were dissected from whole kidneys of male Sprague-Dawley rats which were first perfused in vitro in a recirculating system for 10 to 15 min with a solution containing collagenase. Standard techniques for dissection and perfusion of tALH were followed. Control transepithelial voltage averaged +5.5 +/- 0.5 mV (n = 25). Drug concentration causing 50% inhibition of the voltage (EC50) was determined. EC50 for both MK-196 and furosemide in rat tALH was 8 X 10(-6) M (EC50 for MK-196 in rabbit tALH ws 7 X 10(-5) M). In other experiments, net chloride transport (JCl) in rat tALH averaged 142 +/- 19 pmol.mm-1.min-1 (n = 12), a value nearly twice that reported for the rabbit. In the rat, MK-196 (2 X 10(-4) M) reduced the voltage by 79 +/- 2% and JCl by 76 +/- 13% (n = 6). The same concentration of furosemide inhibited the voltage by 78 +/- 8% and the JCl by 104 +/- 4%(n = 5). Results indicate that: 1) rat tALHs dissected from collagenase-treated kidneys have functional characteristics similar to those reported for the rabbit tALH; and 2) the rat tALH is equally sensitive to MK-196 and furosemide, drugs which act to selectively inhibit active chloride transport.
研究了利尿剂MK - 196（6,7 - 二氯 - 2 - 甲基 - 1 - 氧代 - 2 - 苯基 - 5 - 茚满氧基乙酸）和呋塞米对从大鼠肾脏分离的髓袢升支粗段（tALH）功能的影响。tALH取自雄性Sprague - Dawley大鼠的全肾，这些肾脏首先在体外循环系统中用含胶原酶的溶液灌注10至15分钟。遵循tALH解剖和灌注的标准技术。对照跨上皮电压平均为+5.5±0.5 mV（n = 25）。测定引起电压50%抑制的药物浓度（EC50）。大鼠tALH中MK - 196和呋塞米的EC50均为8×10⁻⁶ M（兔tALH中MK - 196的EC50为7×10⁻⁵ M）。在其他实验中，大鼠tALH中的净氯转运（JCl）平均为142±19 pmol·mm⁻¹·min⁻¹（n = 12），该值几乎是报道的兔的两倍。在大鼠中，MK - 196（2×10⁻⁴ M）使电压降低79±2%，JCl降低76±13%（n = 6）。相同浓度的呋塞米使电压降低78±8%，JCl降低104±4%（n = 5）。结果表明：1）从经胶原酶处理的肾脏分离的大鼠tALH具有与报道的兔tALH相似 的功能特征；2）大鼠tALH对MK - 196和呋塞米同样敏感，这两种药物选择性抑制主动氯转运。
