Diener M, Rummel W
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, F.R.G.
Eur J Pharmacol. 1990 Mar 13;178(1):47-57. doi: 10.1016/0014-2999(90)94792-v.
Distension of the rat colon descendens in vitro by a hydrostatic gradient induced an increase in short-circuit current (Isc). In a mucosa-submucosa preparation containing the plexus submucosus, the increase in Isc was biphasic with a half-time of about 200 s for the spontaneous returning to the baseline. The time course was monophasic in a mucosa preparation without the plexus submucosus. The increase in Isc in the mucosa-submucosa preparation was inhibited by an inhibitor of phospholipase A2, quinacrine, and by indomethacin, tetrodotoxin or atropine; each of these compounds also abolished the second phase of the response. In contrast, only indomethacin was effective in reducing the increase in Isc in the mucosa preparation. In both preparations the response to distension was inhibited by scilliroside, by replacement of Cl- with gluconate, and by administration of frusemide or the chloride channel blocker, anthracene-9-carboxylic acid. The results indicate that distension induces chloride secretion by causing the release of prostaglandins, which act indirectly, i.e. mediated by the submucosal plexus, and directly at the epithelium.
体外通过静水压力梯度扩张大鼠降结肠可引起短路电流(Isc)增加。在含有黏膜下神经丛的黏膜-黏膜下层制备物中,Isc的增加呈双相性,自发恢复到基线的半衰期约为200秒。在没有黏膜下神经丛的黏膜制备物中,时间进程为单相性。黏膜-黏膜下层制备物中Isc的增加受到磷脂酶A2抑制剂喹吖因、吲哚美辛、河豚毒素或阿托品的抑制;这些化合物中的每一种也消除了反应的第二阶段。相比之下,只有吲哚美辛能有效降低黏膜制备物中Isc的增加。在两种制备物中,对扩张的反应都受到海葱糖苷的抑制,用葡萄糖酸盐替代Cl-,以及给予速尿或氯通道阻滞剂蒽-9-羧酸的抑制。结果表明,扩张通过引起前列腺素释放诱导氯分泌,前列腺素通过黏膜下神经丛间接起作用,即介导作用,并且直接作用于上皮细胞。