McCulloch C R, Cooke H J
Department of Physiology, Ohio State University, Columbus 43210.
Regul Pept. 1989 Jan;24(1):87-96. doi: 10.1016/0167-0115(89)90214-0.
The effect of human alpha-calcitonin gene-related peptide (CGRP) on epithelial ion transport was investigated in guinea pig distal colon set up in Ussing flux chambers. Addition of CGRP to the serosal bathing solution evoked a dose-dependent increase in short-circuit current in whole-thickness tissues with intact myenteric and submucosal ganglia, but not in whole-thickness preparations when neural connections between myenteric and submucosal ganglia were severed, nor in sheets of submucosa/mucosa with intact submucosal ganglia. The effects of CGRP were nearly abolished in chloride-free solutions or after treatment with furosemide. Tetrodotoxin and hexamethonium abolished the effects of CGRP on basal short-circuit current whereas atropine did not. CGRP enhanced neurally evoked chloride secretion both in whole thickness and submucosa/mucosa preparations, but the effect in the latter was considerably smaller. These observations suggest that CGRP stimulates chloride secretion primarily by activating myenteric neurons that project either to submucosal ganglia or to the mucosa of the guinea pig distal colon. Furthermore, CGRP appears to have a greater effect on excitability of myenteric neurons than submucosal neurons.
利用Ussing通量室建立豚鼠远端结肠模型，研究人α-降钙素基因相关肽（CGRP）对上皮离子转运的影响。将CGRP添加到浆膜浴液中，可使具有完整肌间和黏膜下神经节的全层组织短路电流呈剂量依赖性增加，但在肌间和黏膜下神经节之间的神经连接被切断的全层制剂中，以及在具有完整黏膜下神经节的黏膜下层/黏膜片中，短路电流并未增加。在无氯溶液中或用呋塞米处理后，CGRP的作用几乎消失。河豚毒素和六甲铵消除了CGRP对基础短路电流的作用，而阿托品则没有。CGRP在全层和黏膜下层/黏膜制剂中均增强了神经诱发的氯离子分泌，但在后者中的作用要小得多。这些观察结果表明，CGRP主要通过激活投射到豚鼠远端结肠黏膜下神经节或黏膜的肌间神经元来刺激氯离子分泌。此外，CGRP对肌间神经元兴奋性的影响似乎比对黏膜下神经元的影响更大
