title: Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients.
abstract: BACKGROUND
  Increased nicotinic receptor mediated relaxation in the gastroesophageal antireflux barrier may be involved in the pathophysiology of reflux. This study is designed to determine whether the defects we previously identified in gastroesophageal reflux disease patients in- vivo are due to abnormalities of the gastric sling, gastric clasp, or lower esophageal circular (LEC) muscle fibers.
  
  
  METHODS
  Muscle strips from whole stomachs and esophagi were obtained from 16 normal donors and 15 donors with histologically proven Barrett's esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or LEC fibers were determined to increasing concentrations of carbachol and to nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor density was measured using subtype selective immunoprecipitation.
  
  
  RESULTS
  Barrett's esophagus gastric sling and LEC fibers have decreased carbachol-induced contractions. Barrett's esophagus sling fibers have decreased M2 -muscarinic receptors and LEC fibers have decreased M3 receptors. Relaxations of all three fiber types are greater in Barrett's esophagus specimens to both high carbachol concentrations and to nicotine following bethanechol precontraction. The maximal response to bethanechol is greater in Barrett esophagus sling and LEC fibers.
  
  
  CONCLUSIONS
  The increased contractile response to bethanechol in Barrett's specimens indicates that the defect is likely not due to the smooth muscle itself. The enhanced nicotinic receptor mediated response may be involved in greater relaxation of the muscles within the high-pressure zone of the gastroesophageal junction during transient lower esophageal sphincter relaxations and during deglutitive inhibition and may be involved in the pathophysiology of gastroesophageal reflux disease.
authors: Department of Medicine, Section of Gastroenterology, North Shore LIJ Health System, Long Island Jewish Medical Center, New Hyde Park, NY, USA.
authors: L S
authors: LS
authors: Miller
authors: A K
authors: AK
authors: Vegesna
authors: A S
authors: AS
authors: Braverman
authors: M F
authors: MF
authors: Barbe
authors: M R
authors: MR
authors: Ruggieri
mesh_terms: D000328:Adult; D001471:Barrett Esophagus / Q000503:physiopathology*; D018723:Bethanechol / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004947:Esophagus / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000503:physiopathology*
chemical_list: D018679:Cholinergic Agonists; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018723:Bethanechol; D009538:Nicotine; D002217:Carbachol
keywords: Barrett's esophagus; gastroesophageal reflux disease; nicotinic receptors; smooth muscle relaxation