Böhme M, Diener M, Rummel W
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
Toxicol Appl Pharmacol. 1992 Jun;114(2):295-301. doi: 10.1016/0041-008x(92)90080-c.
The actions of two mercury compounds, HgCl2 and methyl mercury chloride (MeHg), and of CdCl2 on the epithelium of the rat colon were studied with the whole-cell patch-clamp technique and the Ussing chamber. MeHg (50 microM) induced an increase of membrane outward current (I(out)) in enterocytes of isolated crypts patched from the basolateral side. This action was inhibited by a Cl- channel blocker and a K+ channel blocker, indicating an increase of both the Cl- and the K+ conductance. In contrast, HgCl2 (50 microM) did not affect I(out), whereas CdCl2 (50 microM) decreased it slightly. In mucosal preparations all three compounds induced a concentration-dependent increase in short-circuit current (Isc) when administered to the serosal, i.e., contraluminal side. Sensitivity to chloride transport blockers and anion replacement experiments revealed that the increase in Isc represented Cl- secretion. In contrast to the actions of luminally applied mercury compounds, the increase of tissue conductance (Gt) was only small. Tetrodotoxin and indomethacin suppressed the effect of the metal compounds on Isc and Gt, while atropine diminished it only partly. This indicates that the secretory action of these heavy metals has not only a direct effect on epithelial cells but is also mediated by prostaglandins and cholinergic and noncholinergic neurons.
采用全细胞膜片钳技术和尤斯灌流小室，研究了两种汞化合物氯化汞（HgCl2）和甲基氯化汞（MeHg）以及氯化镉（CdCl2）对大鼠结肠上皮细胞的作用。MeHg（50微摩尔）可使从基底外侧膜片钳制的分离隐窝肠上皮细胞的外向膜电流（I(out)）增加。这种作用可被氯离子通道阻滞剂和钾离子通道阻滞剂抑制，表明氯离子和钾离子电导均增加。相比之下，HgCl2（50微摩尔）对I(out)无影响，而CdCl2（50微摩尔）使其略有降低。在黏膜制剂中，当将这三种化合物施加于浆膜侧（即对腔侧）时，均会引起短路电流（Isc）浓度依赖性增加。对氯离子转运阻滞剂的敏感性和阴离子置换实验表明，Isc的增加代表氯离子分泌。与经腔应用汞化合物的作用不同，组织电导（Gt）的增加很小。河豚毒素和吲哚美辛可抑制金属化合物对Isc和Gt的作用，而阿托品仅部分减弱该作用。这表明这些重金属的分泌作用不仅对上皮细胞有直接影响，还由前列腺素、胆碱能和非胆碱能神经元介导。
