Nobles M, Diener M, Mestres P, Rummel W
Institute for Pharmacology and Toxicology, University of Saarland, Homburg/Saar, Germany.
Acta Physiol Scand. 1991 Jul;142(3):375-86. doi: 10.1111/j.1748-1716.1991.tb09171.x.
The electrolyte transport was compared in proximal and distal segments of the rat colon under control conditions and after induction of secretion on the cAMP-, the cGMP- and the Ca(2+)-pathway. Baseline short-circuit current was decreased by indomethacin and tetrodotoxin in the distal colon, indicating a spontaneous production of neuronally acting prostaglandins. In contrast, baseline short-circuit current in the proximal colon was decreased only by indomethacin, but not by tetrodotoxin. Unidirectional flux measurements revealed that in the distal colon sodium and chloride were absorbed, while the proximal colon secreted chloride. A morphological comparison between the distal and proximal epithelium revealed that the zonulae occludentes and the microvilli were longer in the distal colon. The size of the Golgi apparatus was several times larger in the crypt than in the surface region without differences between proximal and distal colon. Distal segments were more sensitive to an activator of the Ca(2+)-pathway, carbachol, or activators of the cAMP-pathway such as forskolin and a cAMP-analogue. In contrast, the activation of the cGMP-pathway by a cGMP-analogue or by the heat-stable enterotoxin of E. coli (STa) was more effective in the proximal colon. The results give evidence for a segmental specificity with regard to the intracellular pathways responsible for the activation of secretion.
在对照条件下以及通过环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)和钙离子(Ca²⁺)途径诱导分泌后,对大鼠结肠近端和远端节段的电解质转运进行了比较。消炎痛和河豚毒素可降低远端结肠的基线短路电流,表明存在神经元作用的前列腺素的自发产生。相比之下,近端结肠的基线短路电流仅被消炎痛降低,而不被河豚毒素降低。单向通量测量显示,远端结肠吸收钠和氯,而近端结肠分泌氯。远端和近端上皮的形态学比较显示,远端结肠的紧密连接和微绒毛更长。隐窝中高尔基体的大小比表面区域大几倍,近端和远端结肠之间无差异。远端节段对Ca²⁺途径的激活剂卡巴胆碱或cAMP途径的激活剂如福斯高林和一种cAMP类似物更敏感。相比之下,cGMP类似物或大肠杆菌热稳定肠毒素(STa)对cGMP途径的激活在近端结肠中更有效。结果证明了在负责分泌激活的细胞内途径方面存在节段特异性。