Inhibition of ATP levels by quinidine in a human colonic epithelial cell line.
Inhibition of ATP levels by quinidine in a human colonic epithelial cell line.
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奎尼丁对人结肠上皮细胞系中 ATP 水平的抑制作用。
DOI：
10.1152/ajpgi.1986.250.6.g806
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Beuerlein,G
中科院分区：
文献类型：
--
作者：
Dharmsathaphorn,K;Huott,P;Cartwright,CA;McRoberts,JA;Mandel,KG;Beuerlein,G
研究了K+通道阻断剂奎尼丁对血管活性肠肽（VIP）诱导的Cl-分泌的影响。奎尼丁抑制VIP诱导的T84细胞Cl-分泌。在离体人结肠中观察到奎尼丁对Cl-分泌的类似抑制作用。然而，在离体的人结肠，它吸收Na+贪婪，抑制Na+吸收占主导地位。在T84细胞中，奎尼丁的半数最大抑制发生在60 μ M，而300 μ M几乎完全抑制VIP诱导的Cl-分泌。粘液添加奎尼丁至少是同样有效的与丝氨酸相比，除了，表明奎尼丁作用于顶膜或细胞内。奎尼丁在其添加后的第一个15分钟内对VIP刺激的Cl-流出几乎没有影响，这表明顶端膜上Cl-出口途径的阻断是不太可能的机制。同样，奎尼丁没有抑制K+-再循环机制的基底外侧膜在其添加后的第一个15分钟。奎尼丁的初始抑制作用与其降低细胞ATP水平的能力更好地对应。我们的研究表明，细胞ATP水平的耗竭可以解释奎尼丁对肠道电解质转运的初始抑制作用，而后期效应是多因素的。
The influence of quinidine, a putative K+ channel blocker, on Cl- secretion induced by vasoactive intestinal polypeptide (VIP) was investigated. Quinidine inhibited Cl- secretion induced by VIP in T84 cell monolayers. A similar inhibitory effect of quinidine on Cl- secretion was observed in an isolated human colon. However, in the isolated human colon, which absorbs Na+ avidly, inhibition of Na+ absorption predominated. In the T84 cell, the half-maximal inhibition by quinidine occurred at 60 microM, while 300 microM almost completely inhibited the VIP-induced Cl— secretion. Mucosal addition of quinidine was at least equally effective compared with serosal addition, suggesting that quinidine acts on the apical membrane or intracellularly. Quinidine had little or no effect on VIP-stimulated Cl- efflux in the first 15 min after its addition, suggesting that blockage of the Cl- exit pathway on the apical membrane is an unlikely mechanism. Similarly, quinidine did not inhibit the K+-recycling mechanism on the basolateral membrane in the first 15 min after its addition. The initial inhibitory action of quinidine corresponded better with its ability to decrease cellular ATP levels. Our study suggests that the depletion of cellular ATP levels may explain the initial inhibitory action of quinidine on electrolyte transport in the intestine, while the late effect is multifactorial.