Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium

Neurogastroenterol Motil. 2017 Feb;29(2). doi: 10.1111/nmo.12934. Epub 2016 Aug 30.

Abstract

Background: Propofol is a widely used intravenous general anesthetic. Acetylcholine (ACh) is critical in controlling epithelial ion transport. This study was to investigate the effects of propofol on ACh-evoked secretion in rat ileum epithelium.

Methods: The Ussing chamber technique was used to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc).

Key results: Propofol (10-2 -10-6 mol/L) attenuated CCh-evoked Isc of rat ileum mucosa in a dose-dependent manner. The inhibitory effect of propofol was only evident after application to the serosal side. Pretreatment with tetrodotoxin (TTX, 0.3 μmol/L, n=5) had no effect on propofol-induced inhibitory effect, whereas serosal application of K+ channel inhibitor, glibenclamide, but not, an ATP-sensitive K+ channel inhibitor, largely reduced the inhibitory effect of propofol. In addition, pretreatment with either hexamethonium bromide (HB, nicotinic nACh receptor antagonist) or Cl- channel blockers niflumic acid and cystic fibrosis transmembrane conductance regulator (inh)-172 did not produce any effect on the propofol-induced inhibitory effect.

Conclusions & inferences: Propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K+ channels.

Keywords: K+ channels; acetylcholine receptor; intestinal secretion; propofol; short-circuit current.

MeSH terms

  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Carbachol / antagonists & inhibitors
  • Carbachol / pharmacology*
  • Chlorides / antagonists & inhibitors*
  • Chlorides / metabolism
  • Drug Delivery Systems / methods
  • Ileum / drug effects
  • Ileum / metabolism*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Male
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / physiology
  • Propofol / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Anesthetics, Intravenous
  • Chlorides
  • Potassium Channel Blockers
  • Potassium Channels
  • Carbachol
  • Propofol