title: Effects of sphingosine-1-phosphate on pacemaker activity of interstitial cells of Cajal from mouse small intestine.
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 S1P(1,3,4,5) agonist) and SEW 2871 (an S1P(1) agonist) had no effects on pacemaker activity. Suramin (an S1P(3) antagonist) did not block the S1P-induced action on pacemaker currents. However, JTE-013 (an S1P(2) antagonist) blocked the S1P-induced action. RT-PCR revealed the presence of the S1P(2) 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 NH(2)-terminal kinase (JNK) inhibitor II suppressed S1P-induced action. External Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor of endoplasmic reticulum) suppressed action of S1P on ICC. In recording of intracellular Ca(2+) ([Ca(2+)](i)) concentration using fluo-4/AM S1P increased intensity of spontaneous [Ca(2+)](i) oscillations in ICC. These results suggest that S1P can modulate pacemaker activity of ICC through S1P(2) via regulation of external and internal Ca(2+) and mitogenactivated protein kinase activation.
authors.affiliation: Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Kyoung Taek
authors.initials: KT
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Shahi
authors.forename: Dong Chuan
authors.initials: DC
authors.lastname: Zuo
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism; D010755:Organophosphates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081025:Sphingosine-1-Phosphate Receptors; D013498:Suramin / Q000494:pharmacology
chemical_list: D000969:Antinematodal Agents; D004791:Enzyme Inhibitors; C525008:FTY 720P; D007473:Ion Channels; C471998:JTE 013; D008246:Lysophospholipids; D009281:Naphthalenes; D010755:Organophosphates; D011720:Pyrazoles; D011725:Pyridines; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; C533955:sphingosine-1-phosphate receptor-2, mouse; C060506:sphingosine 1-phosphate; D013498:Suramin; D020928:Mitogen-Activated Protein Kinases; C058819:calphostin C; D013110:Sphingosine; D002118:Calcium