Castagliuolo I, LaMont J T, Letourneau R, Kelly C, O'Keane J C, Jaffer A, Theoharides T C, Pothoulakis C
Section of Gastroenterology, Boston University School of Medicine/The University Hospital, Massachusetts.
Gastroenterology. 1994 Sep;107(3):657-65. doi: 10.1016/0016-5085(94)90112-0.
BACKGROUND/AIMS: Activation of intestinal mast cells and neurons is involved in intestinal inflammation and diarrhea. This study compared the effects of neuronal inhibitors and inhibition of intestinal sensory afferent nerves on the intestinal actions of Clostridium difficile toxin A, an inflammatory enterotoxin, and cholera toxin, a noninflammatory enterotoxin.
The effects of lidocaine, hexamethonium, atropine, and long-term pretreatment of capsaicin on fluid secretion, mannitol permeability, myeloperoxidase (MPO) activity, and release of rat mast cell protease II (RMCPII) were measured in toxin A- and cholera toxin-exposed loops in vivo.
Lidocaine, hexamethonium, and capsaicin, but not atropine, inhibited toxin A-mediated secretion and MPO activity, but only capsaicin reduced mannitol permeability. Lidocaine, but not capsaicin, reduced secretion and permeability caused by cholera toxin. Toxin A caused release of RMCPII from rat ileum in vivo and in vitro; this was inhibited by lidocaine or capsaicin, whereas cholera toxin had no effect on release of RMCPII.
Neuronal mechanisms are important in the in vivo effects of these two enterotoxins. Capsaicin-sensitive sensory afferent neurons and mast cells are involved in the intestinal mechanism of toxin A, but not cholera toxin.
背景/目的：肠道肥大细胞和神经元的激活与肠道炎症及腹泻有关。本研究比较了神经元抑制剂以及抑制肠道感觉传入神经对艰难梭菌毒素A（一种炎性肠毒素）和霍乱毒素（一种非炎性肠毒素）肠道作用的影响。
在体内毒素A和霍乱毒素暴露的肠袢中，测量利多卡因、六甲铵、阿托品以及辣椒素长期预处理对液体分泌、甘露醇通透性、髓过氧化物酶（MPO）活性和大鼠肥大细胞蛋白酶II（RMCPII）释放的影响。
利多卡因、六甲铵和辣椒素可抑制毒素A介导的分泌和MPO活性，但阿托品无此作用，且只有辣椒素可降低甘露醇通透性。利多卡因可降低霍乱毒素引起的分泌和通透性，但辣椒素无此作用。毒素A在体内和体外均可引起大鼠回肠RMCPII的释放；这一作用可被利多卡因或辣椒素抑制，而霍乱毒素对RMCPII的释放无影响。
神经元机制在这两种肠毒素的体内作用中起重要作用。辣椒素敏感的感觉传入神经元和肥大细胞参与毒素A的肠道作用机制，但不参与霍乱毒素的肠道作用机制。
