Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium

Life Sci. 2012 Nov 27;91(21-22):1065-9. doi: 10.1016/j.lfs.2012.04.028. Epub 2012 Apr 30.

Abstract

Aims: 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.

Main 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).

Key findings: 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.

Significance: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholinesterase / analysis
  • Acetylcholinesterase / metabolism
  • Animals
  • Cadherins / analysis
  • Cadherins / metabolism
  • Carnitine O-Acetyltransferase / analysis
  • Carnitine O-Acetyltransferase / metabolism
  • Cats
  • Choline O-Acetyltransferase / analysis
  • Choline O-Acetyltransferase / metabolism
  • Cystitis, Interstitial / metabolism
  • Cystitis, Interstitial / veterinary*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Esophagus / cytology
  • Esophagus / metabolism*
  • Membrane Transport Proteins / analysis
  • Membrane Transport Proteins / metabolism
  • Mucous Membrane / cytology
  • Mucous Membrane / metabolism
  • Organic Cation Transport Proteins / analysis
  • Organic Cation Transport Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Muscarinic M2 / analysis
  • Receptor, Muscarinic M2 / metabolism
  • Receptor, Muscarinic M3 / analysis
  • Receptor, Muscarinic M3 / metabolism
  • Vesicular Acetylcholine Transport Proteins / analysis
  • Vesicular Acetylcholine Transport Proteins / metabolism

Substances

  • Cadherins
  • Membrane Transport Proteins
  • Organic Cation Transport Proteins
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Vesicular Acetylcholine Transport Proteins
  • choline transporter
  • Choline O-Acetyltransferase
  • Carnitine O-Acetyltransferase
  • Acetylcholinesterase
  • Acetylcholine