Zhao Wen-Chao, Duan Dong-Xiao, Wang Zhi-Ju, Tang Ning, Yan Ming, Zhang Gui-Hong, Xing Ying
Department of Physiology, Medical School, Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Jpn J Physiol. 2005 Dec;55(6):325-9. doi: 10.2170/jjphysiol.RP000905. Epub 2005 Dec 8.
The present study investigated the underlying cellular mechanism in the effect of ligustrazine (tetramethylpyrazine, TMP) on the anion secretion of colonic mucosa in rats using a short-circuit current (I(sc)) technique in conjunction with "tool drugs." (i) After a pretreatment of the tissues by bathing the bilateral surface with Cl(-)-free Krebs-Henseleit (K-H) solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I(sc), and the total charges transported for 30 min were about 8.7 +/- 1.4 mC/cm(2); an apical pretreatment of DPC and a basolateral addition of acetazolamide decreased the TMP-induced I(sc) by about 60% (P < 0.01) and 45% (P < 0.05), respectively; a basolateral application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), the inhibitor of Na(+)-HCO(3)(-) cotransporter (NBC), did not alter the TMP-induced I(sc). (ii) After the bilateral surface of mucosa was bathed with HCO(3)(-)-free K-H solution for over an hour, a basolateral application of 1 mmol/l TMP produced an increase in I(sc), and the total charges transported in 30 min were about 8.3 +/- 1.9 mC/cm(2); an apical pretreatment of DPC (1 mmol/l), the inhibitor of Cl(-) channels, decreased the TMP-induced Isc by about 84% (P < 0.01). The basolateral presence of bumetanide (0.1 mmol/l), the inhibitor of Na(+)-K(+)-Cl(-) cotransporter (NKCC), significantly reduced the TMP-evoked I(sc) by about 86% (P < 0.01). In conclusion, (i) ligustrazine could promote colonic mucosa secretion Cl(-) via apical Cl(-) channels and basolateral NKCC; (ii) ligustrazine could promote colonic mucosa secretion HCO(3)(-) via apical Cl(-) channels and the basolateral diffusion of CO(2).
本研究采用短路电流（Isc）技术并结合“工具药物”，探讨了川芎嗪（四甲基吡嗪，TMP）对大鼠结肠黏膜阴离子分泌影响的潜在细胞机制。（i）在用无Cl⁻的Krebs-Henseleit（K-H）溶液双侧表面浸泡组织预处理1小时以上后，在基底外侧施加1 mmol/L TMP可使Isc增加，30分钟内转运的总电荷量约为8.7±1.4 mC/cm²；顶端预处理DPC并在基底外侧添加乙酰唑胺分别使TMP诱导的Isc降低约60%（P<0.01）和45%（P<0.05）；基底外侧施加Na⁺-HCO₃⁻共转运体（NBC）抑制剂4,4'-二异硫氰酸芪-2,2'-二磺酸（DIDS），未改变TMP诱导的Isc。（ii）在用无HCO₃⁻的K-H溶液双侧表面浸泡黏膜1小时以上后，在基底外侧施加1 mmol/L TMP可使Isc增加，30分钟内转运的总电荷量约为8.3±1.9 mC/cm²；顶端预处理Cl⁻通道抑制剂DPC（1 mmol/L）使TMP诱导的Isc降低约84%（P<0.01）。基底外侧存在Na⁺-K⁺-Cl⁻共转运体（NKCC）抑制剂布美他尼（0.1 mmol/L）可使TMP诱发的Isc显著降低约86%（P<0.01）。总之，（i）川芎嗪可通过顶端Cl⁻通道和基底外侧NKCC促进结肠黏膜分泌Cl⁻；（ii）川芎嗪可通过顶端Cl⁻通道和基底外侧CO₂扩散促进结肠黏膜分泌HCO₃⁻。
