川芎嗪增加大鼠远端结肠阴离子分泌的基侧膜机制

本研究用短路电流技术来观察在川芎嗪作用下,电解质在大鼠远端结肠上皮细胞的转运及其细胞机制。在新鲜分离的结肠上皮的基侧膜加入川芎嗪,能产生较大的短路电流。用粘膜下神经元阻断剂——河豚毒素预作用于结肠上皮,不影响随后的川芎嗪所产生的短路电流,前列腺素合成抑制剂indomethacin预作用可使随后的川芎嗪产生的短路电流减少55．2％。在结肠上皮的顶膜加入Cl^-通道阻断剂DPC和glibenclamide,能完全阻断川芎嗪产生的短路电流。Bumetanide,基侧膜钠、钾、氯共转运体阻断剂能抑制川芎嗪引起的短路电流的85．2％,而结肠上皮细胞基侧膜的非选择性钾通道阻断剂Ba^2 能阻断90％以上的短路电流,说明基侧膜的钠、钾、氯共转运体和钾通道在川芎嗪引起的短路电流中起着重要的作用。上述结果表明,川芎嗪刺激大鼠远端结肠上皮细胞分泌Cl^-是通过上皮细胞顶膜Cl^-通道和基侧膜的钠、钾、氯共转体和K^ 通道介导的。

Basolateral membrane mechanisms involved in ligustrazine-stimulated anion secretion in rat distal colon

The present study investigated the cellular mechanism underlying the effect of ligustrazine on the ion transport in rat distal colon using the short-circuit current (ISC ) technique. In freshly isolated colonic strips, basolateral addition of ligustrazine stimulated a rise in ISC, which was resistant to basolateral application of neuronal sodium channel blocker tetrodotoxin (TTX) , but inhibited by 55. 2% by basolateral pretreatment with prostaglandin inhibitor indomethacin. The ligustrazine-in-duced ISC increase was inhibited by apical application of C1 channel blockers diphenylamine-2,2'-dicarboxylic acid (DPC) and glibenclamide. Basolaterally administered bumetanide, an inhibitor of Na +-K +-2C1 -cotransporter, inhibited ligustrazine-evoked current increases by 85. 2% and basolateral exposure to Ba2+ , a non-specific potassium channels blocker, and blocked the current by more than 90% , indicating that basolateral Na+-K+ -2C1- cotransporter and K+ channels played an important role in the effect of ligustrazine. The results suggested that ligustrazine could stimulate rat distal colon C1- secretion that is mediated by basolateral Na + -K + -2C1 cotransporter and K + channel.