Inhibition of colonic Na+ transport by amiloride analogues.
Inhibition of colonic Na+ transport by amiloride analogues.
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阿米洛利类似物抑制结肠钠转运。
DOI：
10.1152/ajpcell.1989.256.1.c67
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Benos,DJ
中科院分区：
文献类型：
--
作者：
Bridges,RJ;CragoeJr,EJ;Frizzell,RA;Benos,DJ
比较了几种阿米洛利类似物抑制地塞米松治疗大鼠结肠中生电 Na+ 转运的效力。在地塞米松治疗的大鼠中测定了跨结肠粘膜的短路电流（Isc）和结肠肠上皮细胞膜囊泡对 22Na+ 的摄取。 Isc 和 22Na+ 摄取抑制的动力学分析揭示了高亲和力和低亲和力阿米洛利途径的存在。一种途径对苯扎米尔 (15.5 nM; 5.4 nM)、苯那米尔 (19.4 nM; 7.0 nM)、3',4'-二氯苯扎米尔 (29.0 nM; 25.2 nM) 和阿米洛利 (115 nM; 12.4 nM) 具有高亲和力 [(Ki-Isc; Ki 摄取]，但对5-(N-乙基-N-异丙基)阿米洛利 (EIPA)（大于 100 µM；大于 9.9 µM）和 5-(N-丙基-N-丁基)-2'-4'-二氯苯甲酰胺 (PBDCB)（大于 µM；大于 32.8 µM）。高亲和力途径占 Na+ 转运的 75-83%。对每种类似物的亲和力较低（例如，阿米洛利 Ki-Isc 1 microM；Ki 摄取 4 microM），仅占 Na+ 转运的 15-25%。结果表明，这些阿米洛利类似物对高亲和力途径的结构抑制模式是在其他产电 Na+ 转运上皮细胞中观察到的模式，并且这种药理学特征保留在源自膜泡的膜囊泡中。此外，还研究了 EIPA 和苯扎米尔抑制正常大鼠（即未用地塞米松治疗）穿过结肠的电中性 Na+ 转运的效力。（摘要截短为 250 字）
The potency of several amiloride analogues to inhibit electrogenic Na+ transport in colon from dexamethasone-treated rats was compared. Short-circuit current (Isc) across the colonic mucosa and 22Na+ uptake into membrane vesicles derived from colonic enterocytes was determined in dexamethasone-treated rats. Kinetic analysis of inhibition of Isc and 22Na+ uptake revealed the presence of a high- and low-affinity amiloride pathway. One pathway had a high affinity [(Ki-Isc; Ki uptake] to benzamil (15.5 nM; 5.4 nM), phenamil (19.4 nM; 7.0 nM), 3',4'-dichlorobenzamil (29.0 nM; 25.2 nM), and amiloride (115 nM; 12.4 nM) but a much lower affinity to 5-(N-ethyl-N-isopropyl)amiloride (EIPA) (greater than 100 microM; greater than 9.9 microM) and 5-(N-propyl-N-butyl)-2'-4'-dichlorobenzamil (PBDCB) (greater than microM; greater than 32.8 microM). The high-affinity pathway accounted for 75-83% of the transport of Na+. The second pathway had nearly the same low affinity for each of the analogues (e.g., amiloride Ki-Isc 1 microM; Ki uptake 4 microM) and accounted for only 15-25% of the transport of Na+. The results demonstrate that the structure-inhibitory pattern of these amiloride analogues for the high-affinity pathway is the pattern observed in other electrogenic Na+-transporting epithelia and that this pharmacological profile is preserved in membrane vesicles derived from colonic enterocytes. In addition, the potency of EIPA and benzamil to inhibit electroneutral Na+ transport across the colon from normal rats (i.e., not treated with dexamethasone) was also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)