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

• Published in: Molecules and cells 2013, 35(1), , pp.79-86
• Main Authors: Kim, Y.D., Chosun University, Gwangju, Republic of Korea, Han K.T., Chosun University, Gwangju, Republic of Korea, Lee, J., Chosun University, Gwangju, Republic of Korea, Park, C.G., Chosun University, Gwangju, Republic of Korea, Kim, M.Y., Chosun University, Gwangju, Republic of Korea, Shahi, P.K., Chosun University, Gwangju, Republic of Korea, Zuo, D.C., Chosun University, Gwangju, Republic of Korea, Choi, S., Chosun University, Gwangju, Republic of Korea, Jun, J.Y., Chosun University, Gwangju, Republic of Korea
• Format: Article
• Language: English
• Subjects: Animals; Antinematodal Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calcium - metabolism; Cell Biology; Cells, Cultured; Enzyme Inhibitors - pharmacology; Female; GASTROINTESTINAL MOTILITY; Interstitial Cells of Cajal - cytology; Interstitial Cells of Cajal - drug effects; Interstitial Cells of Cajal - metabolism; interstitial cells of Cajal,pacemaker activity,sphingosine-1-phosphate; Intestine, Small - cytology; Intestine, Small - drug effects; Intestine, Small - metabolism; Ion Channels - drug effects; Ion Channels - metabolism; Life Sciences; Lysophospholipids - pharmacology; Male; Membrane Potentials - drug effects; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; MOTRICITE GASTRO-INTESTINALE; MOVILIDAD GASTROINTESTINAL; Naphthalenes - metabolism; Organophosphates - pharmacology; Patch-Clamp Techniques; Pyrazoles - pharmacology; Pyridines - pharmacology; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - metabolism; Research Article; Signal Transduction - drug effects; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Sphingosine-1-Phosphate Receptors; Suramin - pharmacology; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-013-2282-0

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.