Department of Physiology and Cell Biology and Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Curr Opin Gastroenterol. 2010 Mar;26(2):102-8. doi: 10.1097/MOG.0b013e328334df4f.
The enteric nervous system integrates secretion and motility into homeostatic patterns of behavior susceptible to disorder. Progress in understanding mechanosensory detection in these processes, disordered enteric nervous system integration in diarrhea and constipation and pharmacotherapy is summarized.
Most neurons in the enteric nervous system discharge in response to distortion. Drugs acting directly to open chloride conductance channels in the mucosal epithelium are therapeutic options for constipation.
Mechanoreception is required for negative feedback control. At issue is identification of the neurons that fulfil the requirement for mechanoreception. Understanding secretomotor neurons is basic to understanding neurogenic secretory diarrhea and constipation and therapeutic strategies. A strategy for treatment of chronic constipation is development of agents that act directly to open Cl channels, which thereby increases the liquidity of the luminal contents. Lubiprostone, a recently Food and Drug Administration-approved drug, increases intraluminal liquidity by opening Cl channels. The future for the drug is clouded by controversy over whether its action is directly at one or the other of chloride channel type 2 (ClC-2) or cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels or both and whether action reflects involvement of G protein-coupled prostaglandin receptors expressed by mucosal epithelial cells.
肠神经系统将分泌和运动整合到易发生紊乱的自主行为模式中。本文总结了在这些过程中对机械感觉检测、肠神经系统紊乱导致的腹泻和便秘以及药物治疗的理解方面的进展。
肠神经系统中的大多数神经元对变形有反应。直接作用于黏膜上皮细胞氯离子通道开放的药物是治疗便秘的选择。
机械感觉是负反馈控制所必需的。问题是确定满足机械感觉要求的神经元。了解分泌运动神经元是理解神经源性分泌性腹泻和便秘以及治疗策略的基础。治疗慢性便秘的策略是开发直接作用于开放 Cl 通道的药物,从而增加腔内容物的流动性。鲁比前列酮是一种最近获得美国食品和药物管理局批准的药物,通过打开 Cl 通道增加腔内的流动性。该药物的未来因争议而蒙上阴影,即其作用是直接作用于氯离子通道 2(ClC-2)或囊性纤维化跨膜电导调节剂(CFTR)氯离子通道中的一种或两种,以及作用是否反映表达于黏膜上皮细胞的 G 蛋白偶联前列腺素受体的参与。