Molecules and Cells

, Volume 35, Issue 1, pp 79–86

Effects of sphingosine-1-phosphate on pacemaker activity of interstitial cells of Cajal from mouse small intestine

Authors

  • Young Dae Kim
    • Department of Internal Medicine, College of MedicineChosun University
  • Kyoung Taek Han
    • Department of Internal Medicine, College of MedicineChosun University
  • Jun Lee
    • Department of Internal Medicine, College of MedicineChosun University
  • Chan Guk Park
    • Department of Internal Medicine, College of MedicineChosun University
  • Man Yoo Kim
    • Department of Internal Medicine, College of MedicineChosun University
  • Pawan Kumar Shahi
    • Department of PhysiologyChosun University
  • Dong Chuan Zuo
    • Department of PhysiologyChosun University
  • Seok Choi
    • Department of PhysiologyChosun University
    • Department of PhysiologyChosun University
Research Article

DOI: 10.1007/s10059-013-2282-0

Cite this article as:
Kim, Y.D., Han, K.T., Lee, J. et al. Mol Cells (2013) 35: 79. doi:10.1007/s10059-013-2282-0

Abstract

Interstitial cells of Cajal (ICC) are the pacemaker cells that generate the rhythmic oscillation responsible for the production of slow waves in gastrointestinal smooth muscle. Spingolipids are known to present in digestive system and are responsible for multiple important physiological and pathological processes. In this study, we are interested in the action of sphingosine 1-phosphate (S1P) on ICC. S1P depolarized the membrane and increased tonic inward pacemaker currents. FTY720 phosphate (FTY720P, an S1P1,3,4,5 agonist) and SEW 2871 (an S1P1 agonist) had no effects on pacemaker activity. Suramin (an S1P3 antagonist) did not block the S1P-induced action on pacemaker currents. However, JTE-013 (an S1P2 antagonist) blocked the S1P-induced action. RT-PCR revealed the presence of the S1P2 in ICC. Calphostin C (a protein kinase C inhibitor), NS-398 (a cyclooxygenase-2 inhibitor), PD 98059 (a p42/44 inhibitor), or SB 203580 (a p38 inhibitor) had no effects on S1P-induced action. However, c-jun NH2-terminal kinase (JNK) inhibitor II suppressed S1P-induced action. External Ca2+-free solution or thapsigargin (a Ca2+-ATPase inhibitor of endoplasmic reticulum) suppressed action of S1P on ICC. In recording of intracellular Ca2+ ([Ca2+]i) concentration using fluo-4/AM S1P increased intensity of spontaneous [Ca2+]i oscillations in ICC. These results suggest that S1P can modulate pacemaker activity of ICC through S1P2 via regulation of external and internal Ca2+ and mitogenactivated protein kinase activation.

Keywords

interstitial cells of Cajalintestinal motilitypacemaker activitysphingosine-1-phosphate

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2013