Molecules and Cells

, Volume 33, Issue 5, pp 509–516

Neurotensin modulates pacemaker activity in interstitial cells of Cajal from the mouse small intestine

  • Jun Lee
  • Young Dae Kim
  • Chan Guk Park
  • Man Yoo Kim
  • In Yeoub Chang
  • Dong Chuan Zuo
  • Pawan Kumar Shahi
  • Seok Choi
  • Cheol Ho Yeum
  • Jae Yeoul Jun
Article

DOI: 10.1007/s10059-012-2290-5

Cite this article as:
Lee, J., Kim, Y.D., Park, C.G. et al. Mol Cells (2012) 33: 509. doi:10.1007/s10059-012-2290-5

Abstract

Neurotensin, a tridecapeptide localized in the gut to discrete enteroendocrine cells of the small bowel mucosa, is a hormone that plays an important role in gastrointestinal secretion, growth, and motility. Neurotensin has inhibitory and excitatory effects on peristaltic activity and produces contractile and relaxant responses in intestinal smooth muscle. Our objective in this study is to investigate the effects of neurotensin in small intestinal interstitial cells of Cajal (ICC) and elucidate the mechanism. To determine the electrophysiological effects of neurotensin on ICC, whole-cell patch clamp recordings were performed in cultured ICC from the small intestine. Exposure to neurotensin depolarized the membrane of pacemaker cells and produced tonic inward pacemaker currents. Only neurotensin receptor1 was identified when RT-PCR and immunocytochemistry were performed with mRNA isolated from small intestinal ICC and c-Kit positive cells. Neurotensin-induced tonic inward pacemaker currents were blocked by external Na+-free solution and in the presence of flufenamic acid, an inhibitor of non-selective cation channels. Furthermore, neurotensin-induced action is blocked either by treatment with U73122, a phospholipase C inhibitor, or thapsigargin, a Ca2+-ATPase inhibitor in ICC. We found that neurotensin increased spontaneous intracellular Ca2+ oscillations as seen with fluo4/AM recording. These results suggest that neurotensin modulates pacemaker currents via the activation of non-selective cation channels by intracellular Ca2+-release through neurotensin receptor1.

Keywords

gastrointestinal motilityinterstitial cells of Cajalneurotensinneurotensin receptor1

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2012

Authors and Affiliations

  • Jun Lee
    • 2
  • Young Dae Kim
    • 2
  • Chan Guk Park
    • 2
  • Man Yoo Kim
    • 2
  • In Yeoub Chang
    • 3
  • Dong Chuan Zuo
    • 1
  • Pawan Kumar Shahi
    • 1
  • Seok Choi
    • 1
  • Cheol Ho Yeum
    • 1
  • Jae Yeoul Jun
    • 1
  1. 1.Department of Physiology, College of MedicineChosun UniversityGwangjuKorea
  2. 2.Department of Internal Medicine, College of MedicineChosun UniversityGwangjuKorea
  3. 3.Department of Anatomy, College of MedicineChosun UniversityGwangjuKorea