Heinke B, Hörger S, Diener M
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany.
Eur J Pharmacol. 1998 Dec 4;362(2-3):199-206. doi: 10.1016/s0014-2999(98)00785-7.
The effect of carbachol, an agonist of the Ca2+ pathway, on K+ transport in rat proximal and distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb+, a marker for K+, in mucosa-submucosa preparations. Unidirectional ion flux measurements revealed that carbachol stimulated K+ secretion in the proximal colon by a marked increase in the serosa-to-mucosa flux (J(Rb)sm) and a more moderate rise in the mucosa-to-serosa flux (J(Rb)ms). In the distal colon carbachol had no effect on J(Rb)ms but J(Rb)sm was reduced after a transient increase finally resulting in an inhibition of K+ secretion. Carbachol caused a stimulation of mucosal Rb+ uptake in the distal colon, which was diminished in the presence of inhibitors of the apical H+-K+-ATPase, vanadate and ouabain. In contrast, in the proximal colon the serosal Rb+ uptake was enhanced by carbachol, an effect, which could be prevented by bumetanide, an inhibitor of the basolateral Na+-K+-2Cl(-)-cotransporter. Efflux experiments revealed that carbachol caused a transient increase of apical and basolateral Rb+ permeability in both colonic segments. In the distal colon, stimulated K+ efflux to the serosal side was reduced by quinine, efflux to the mucosal side was blocked by tetraethylammonium. In the proximal colon, carbachol-activated apical and basolateral K+ efflux were inhibited by Ba2+. In conclusion, these data suggest that in the distal colon carbachol stimulates the H+-K+-ATPase and the basolateral K+ efflux through quinine-sensitive K+ channels, whereas in the proximal colon carbachol induces K+ secretion due to a stimulation of the basolateral Na+-K+-2Cl(-)-cotransporter and an increased efflux to the luminal side via Ba2+-sensitive apical K+ channels.
通过测量大鼠近端和远端结肠黏膜 - 黏膜下层制剂中钾离子（K⁺）的标志物铷离子（Rb⁺）的单向通量、摄取和流出，研究了Ca²⁺途径激动剂卡巴胆碱对大鼠近端和远端结肠K⁺转运的影响。单向离子通量测量显示，卡巴胆碱通过显著增加浆膜到黏膜的通量（J(Rb)sm）和更适度地增加黏膜到浆膜的通量（J(Rb)ms）来刺激近端结肠的K⁺分泌。在远端结肠，卡巴胆碱对J(Rb)ms没有影响，但J(Rb)sm在短暂增加后降低，最终导致K⁺分泌受到抑制。卡巴胆碱刺激远端结肠黏膜对Rb⁺的摄取，在顶端H⁺ - K⁺ - ATP酶抑制剂钒酸盐和哇巴因存在时这种摄取减少。相反，在近端结肠，卡巴胆碱增强了浆膜对Rb⁺的摄取，这种作用可被基底外侧Na⁺ - K⁺ - 2Cl⁻协同转运体抑制剂布美他尼阻止。流出实验显示，卡巴胆碱导致两个结肠段顶端和基底外侧Rb⁺通透性短暂增加。在远端结肠，奎宁减少了刺激的K⁺向浆膜侧的流出，四乙铵阻止了K⁺向黏膜侧的流出。在近端结肠，卡巴胆碱激活的顶端和基底外侧K⁺流出被Ba²⁺抑制。总之，这些数据表明，在远端结肠，卡巴胆碱通过奎宁敏感的K⁺通道刺激H⁺ - K⁺ - ATP酶和基底外侧K⁺流出，而在近端结肠，卡巴胆碱由于刺激基底外侧Na⁺ - K⁺ - 2Cl⁻协同转运体并通过Ba²⁺敏感的顶端K⁺通道增加向管腔侧的流出而诱导K⁺分泌。
