Enteric nervous system: sensory physiology, diarrhea and constipation.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Wood
Jackie D
JD
Department of Physiology and Cell Biology and Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA. wood.13@osu.edu
D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D018118:Chloride Channels / Q000378:metabolism / Q000502:physiology; D003248:Constipation / Q000188:drug therapy / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism* / Q000502:physiology; D003967:Diarrhea / Q000188:drug therapy / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism; D000068238:Lubiprostone; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012680:Sensitivity and Specificity
D018118:Chloride Channels; D018078:Receptors, Prostaglandin E; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000068238:Lubiprostone; D000527:Alprostadil