Research Article

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

  • Young Dae KimAffiliated withDepartment of Internal Medicine, College of Medicine, Chosun University
  • , Kyoung Taek HanAffiliated withDepartment of Internal Medicine, College of Medicine, Chosun University
  • , Jun LeeAffiliated withDepartment of Internal Medicine, College of Medicine, Chosun University
  • , Chan Guk ParkAffiliated withDepartment of Internal Medicine, College of Medicine, Chosun University
  • , Man Yoo KimAffiliated withDepartment of Internal Medicine, College of Medicine, Chosun University
  • , Pawan Kumar ShahiAffiliated withDepartment of Physiology, Chosun University
  • , Dong Chuan ZuoAffiliated withDepartment of Physiology, Chosun University
  • , Seok ChoiAffiliated withDepartment of Physiology, Chosun University
  • , Jae Yeoul JunAffiliated withDepartment of Physiology, Chosun University Email author 

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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 Cajal intestinal motility pacemaker activity sphingosine-1-phosphate