Role of mast cell-derived mediators in acid-induced shortening of the esophagus.
It has recently been demonstrated that acid-induced esophageal mucosal injury leads to esophageal shortening, raising the possibility that reflux esophagitis per se may contribute to the development of hiatal hernia. The aim of the present study was to determine whether mast cell-derived mediators are involved in this acid-induced esophageal shortening. Changes in esophageal length were continuously monitored in anesthetized opossums while the esophageal lumen was perfused with 100 mmol/l HCl or normal saline. Changes in esophageal length were compared between animals perfused with acid, with or without pretreatment with the mast cell stabilizers doxantrazole or disodium cromoglycate (DSCG), and animals perfused with normal saline, with or without pretreatment with DSCG. In separate in vitro studies the effect of the mast cell stabilizers on electrical field stimulation-induced esophageal longitudinal muscle contraction was determined. Gradual esophageal lengthening occurred during saline perfusion, irrespective of whether animals were pretreated with DSCG. In contrast, acid perfusion induced esophageal shortening, which was abolished by pretreatment with either doxantrazole or DSCG in doses sufficient to attenuate the acid-induced mucosal histamine release. In vitro, the mast cell stabilizers had no effect on electrical field stimulation-induced esophageal shortening. This study suggests that esophageal shortening associated with acute acid-induced esophageal mucosal injury in the opossum is dependent on mast cell-derived mediators.
Paterson
W G
WG
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada.
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000139:chemically induced; D004205:Cromolyn Sodium / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004848:Epithelium / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005744:Gastric Acid; D005764:Gastroesophageal Reflux / Q000473:pathology; D006636:Histamine Release; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009893:Opossums; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D001993:Bronchodilator Agents; D013892:Thioxanthenes; D044004:Xanthones; D004205:Cromolyn Sodium; D006851:Hydrochloric Acid; C010134:doxantrazole