GPR39 is coupled to TMEM16A in intestinal fibroblast-like cells

PLoS One. 2012;7(10):e47686. doi: 10.1371/journal.pone.0047686. Epub 2012 Oct 25.

Abstract

GPR39 is a GPCR implicated as a regulator of gastrointestinal motility, although the mechanism remains elusive. Here, we report that GPR39 is expressed by a specific cell population cultured from mouse small intestine muscle layers, which was subsequently identified as fibroblast-like cells (FLCs) that have recently been shown to modulate gut motility. Application of the GPR39 agonist, Zn(2+), induced large currents and membrane depolarization in FLCs cultured from wild-type mice, but not Gpr39(-/-) mice. This Zn(2+)-induced current could be suppressed by application of a TMEM16A antagonist, CaCC(inh)-A01, or by silencing Tmem16a expression. These data suggest that GPR39 might modulate gut motility via regulating TMEM16A function in FLCs.

MeSH terms

  • Animals
  • Anoctamin-1
  • Chloride Channels / metabolism*
  • Electrophysiology / methods
  • Fibroblasts / cytology*
  • Gastrointestinal Motility
  • Gastrointestinal Tract / cytology*
  • Gene Expression Regulation*
  • Gene Silencing
  • Immunohistochemistry / methods
  • Intestine, Small / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Neurons
  • RNA, Small Interfering / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Zinc / chemistry

Substances

  • ANO1 protein, mouse
  • Anoctamin-1
  • Chloride Channels
  • GPR39 protein, mouse
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Zinc

Grant support

The authors have no support or funding to report.