A three-tiered defense system exists in the esophagus, which serves a dual
purpose of both limiting the degree of gastroesophageal reflux and minimizi
ng the risk of acid-induced mucosal injury. The antireflux barrier, compose
d of both the lower esophageal sphincter and the diaphragmatic pinch-cock,
is the first line of defense and serves to limit the frequency and volume o
f refluxed gastric contents. When the antireflux barrier fails, the second
line of defense, esophageal clearance, comes into play and serves to limit
the duration of contact between gastric contents and the esophageal epithel
ium. Mechanisms involved in esophageal clearance include gravity and esopha
geal peristalsis, which remove volume, and secretions from swallowed saliva
and esophageal submucosal glands, which neutralize acid. The third line of
defense, tissue resistance, is necessary when acid contact time is prolong
ed such as when esophageal clearance is either ineffective or not operative
(e.g., during sleep). Most studies that have examined esophageal clearance
mechanisms have focused on the roles of esophageal peristalsis and salivar
y secretion, but the role of submucosal gland secretions is less well under
stood. This article reviews the structure and function of esophageal submuc
osal glands and discusses the potential role of their secretory products in
esophageal clearance and tissue resistance. (C) 1999 by Am. Cell. of Gastr
oenterology.