title: Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium.
abstract: OBJECTIVE
  A non-neuronal cholinergic system has been described in epithelial cells including that of the urinary bladder (urothelium) and the upper gastrointestinal tract (esophagus). Epithelial dysfunction has been implicated in the pathophysiology of persistent pain conditions such as painful bladder syndrome as well as functional heartburn. For example, alterations in the ability to synthesize and release acetylcholine may contribute to changes in epithelial sensory and barrier function associated with a number of functional genitourinary and intestinal disorders.
  
  
  METHODS
  We examined using immunoblot, acetylcholine (ACh)-synthesis and release components in cat esophageal mucosa and whether elements of these components are altered in a naturally occurring model of chronic idiopathic cystitis termed feline interstitial cystitis (FIC).
  
  
  RESULTS
  We identified proteins involved in ACh synthesis and release (high affinity choline transporter, CHT1; ACh synthesizing enzyme choline acetyltransferase ChAT and carnitine acetyltransferase CarAT; vesicular ACh transporter VAChT and the organic cation transporter isoforms 1-3 or OCT-1-3) in cat esophageal mucosa. Significant alterations in CHT, ChAT, VAChT and OCT-1 were detected in the esophageal mucosa from FIC cats. Changes in the vesicular nucleotide transporter (VNUT) and the junctional protein pan-cadherin were also noted.
  
  
  CONCLUSIONS
  Taken together, these findings suggest that changes in the non-neuronal cholinergic system may contribute to alterations in cell-cell contacts and possibly communication with underlying cells that may contribute to changes in sensory function and visceral hyperalgesia in functional esophageal pain.
authors.affiliation: University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Wolf-Johnston
authors.forename: Ann T
authors.initials: AT
authors.lastname: Hanna-Mitchell
authors.forename: Charles A
authors.initials: CA
authors.lastname: Buffington
authors.forename: Sunita
authors.initials: S
authors.lastname: Shinde
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.forename: Emeran
authors.initials: E
authors.lastname: Mayer
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002332:Carnitine O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D002415:Cats; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D018856:Cystitis, Interstitial / Q000378:metabolism / Q000662:veterinary*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004947:Esophagus / Q000166:cytology / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000032:analysis / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000032:analysis / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D015820:Cadherins; D026901:Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D050494:Vesicular Acetylcholine Transport Proteins; C065637:choline transporter; D002795:Choline O-Acetyltransferase; D002332:Carnitine O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine