생쥐 소장에서 분리된 Interstitial Cells of Cajal에 대한 Sphingosine Mono-Phosphate의 작용 및 기전

Abstract

ABSTRACT Effects of Sphingoshine Mono-Phosphate on Pacemaker Activity in Interstitial Cells of Cajal from Murine Small Intestine Han Kyoung-Taek Advisor : Prof. Kim Man-Woo Ph.D. Department of Medicine, Graduate School of Chosun University

Several reports demonstrated the diverse action of Sphingosine mono-phosphate (S1P) at the level of many tissues or single cell. Especially, actions on S1P receptors showed several effects in neuronal and non-neuronal systems. The functional study was investigated to determine whether S1P modulates pacemaker currents generated in interstitial cells of Cajal (ICC) of murine small intestine by using a whole cell patch clamp techniques at 30 °C. Externally applied S1P produced membrane depolarization in the current-clamp mode and increased tonic inward pacemaker currents in the voltage-clamp mode. Pretreatment of suramin did not block the S1P-induced effects on pacemaker currents. And externally applied SEW-2871 and FTY-720 did not have function on pacemaker currents. However, pretreatment of JTE-013 blocked the action of S1P on pacemaker currents. External Na+-free solution abolished the generation of pacemaker currents and inhibited the S1P-induced tonic inward currents. Futhermore, the pretreatment with Ca2+-free solution and thapsigargin abolished the generation of pacemaker currents and suppressed the S1P-induced action on ICC. These results suggest that S1P modulates the pacemaker activities through S1P2 receptor activation in ICC by external Ca2+ influx and internal Ca2+ release. Therefore, the ICC are target for S1P and their interaction can affect intestinal motility.