16-16-dimethylprostaglandin-e2 and zinc-chloride

Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue (

Topics: 16,16-Dimethylprostaglandin E2; Animals; Bumetanide; Chloride Channel Agonists; Chloride Channels; Chlorides; Cystic Fibrosis Transmembrane Conductance Regulator; Dose-Response Relationship, Drug; Esophageal Mucosa; Female; Gene Expression Regulation; Hydrochloric Acid; Lubiprostone; Male; Occludin; Swine; Time Factors; Zinc Compounds