| We have recently discovered that a
Phospholipase A2, an enzyme similar to a lipid digesting enzyme
secreted by the pancreas, is present in the circular muscle
layer of the LES and produces arachidonic acid, presumably by
digesting selected phospholipids from the muscle cell membrane.
Arachidonic acid metabolites, such as prostaglandin F2a and
thromboxane A2, contribute to maintaining LES tone by binding
to selective receptors on the cell membrane. These signal transduction
pathways are altered by inflammation, as it occurs in gastroesophageal
reflux disease.
Our research is
focused on identifying the phospholipase A2 present in the
LES, understanding the mechanisms regulating its production
and activity, and defining inflammation-induced changes in
this signal transduction pathway.
Selected Publications:
Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. HCl-Induced Inflammatory Mediators in Cat Esophageal Mucosa and Inflammatory Mediators in Esophageal Circular Muscle in an In Vitro Model of Esophagitis. Am J Physiol Gastrointest Liver Physiol. 2006 Jan 26;
Xiao ZL, Cao W, Biancani P, Behar J. Non-Genomic Effects of Progesterone on the Contraction of Muscle Cells from Guinea Pig Colon. Am J Physiol Gastrointest Liver Physiol. 2006 Jan 6;
Cheng L, Harnett KM, Cao W, Liu F, Behar J, Fiocchi C, Biancani P. Hydrogen peroxide reduces lower esophageal sphincter tone in human esophagitis. Gastroenterology. 2005 Nov;129(5):1675-85.
Cheng L, Cao W, Fiocchi C, Behar J, Biancani P, Harnett KM. In vitro model of acute esophagitis in the cat. Am J Physiol Gastrointest Liver Physiol. 2005 Nov;289(5):G860-9. Epub 2005 Jul 21.
Xiao ZL, Pricolo V, Biancani P, Behar J. Role of progesterone signaling in the regulation of G-protein levels in female chronic constipation. Gastroenterology. 2005 Mar;128(3):667-75.
Harnett KM, Cao W, Biancani P. Signal-transduction pathways that regulate smooth muscle function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles. Am J Physiol Gastrointest Liver Physiol. 2005 Mar;288(3):G407-16.
Cheng L, Cao W, Behar J, Biancani P, Harnett KM. Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle. Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G787-97. Epub 2004 Nov 18.
Cao W, Cheng L, Behar J, Fiocchi C, Biancani P, Harnett KM. Proinflammatory cytokines alter/reduce esophageal circular muscle contraction in experimental cat esophagitis. Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1131-9. Epub 2004 Jul 22.
Kim N, Cao W, Song IS, Kim CY, Harnett KM, Cheng L, Walsh MP, Biancani P. Distinct kinases are involved in contraction of cat esophageal and lower esophageal sphincter smooth muscles. Am J Physiol Cell Physiol. 2004 Aug;287(2):C384-94. Epub 2004 May 5.
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