Biomol Ther 2018; 26(6): 546-552
Effect of Sphingosine-1-Phosphate on Intracellular Free Ca2+ in Cat Esophageal Smooth Muscle Cells
Dong Kyu Lee1,†, Young Sil Min2,†, Seong Su Yoo1, Hyun Sub Shim1, Sun Young Park1 and Uy Dong Sohn1,*
1Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 06911,
2Department of Pharmaceutical Engineering, College of Convergence Science and Technology, Jung Won University, Goesan 28054, Republic of Korea
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†The first two authors contributed equally to this work.
Received: March 22, 2018; Revised: May 4, 2018; Accepted: May 8, 2018; Published online: June 19, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

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A comprehensive collection of proteins senses local changes in intracellular Ca2+ concentrations ([Ca2+]i) and transduces these signals into responses to agonists. In the present study, we examined the effect of sphingosine-1-phosphate (S1P) on modulation of intracellular Ca2+ concentrations in cat esophageal smooth muscle cells. To measure [Ca2+]i levels in cat esophageal smooth muscle cells, we used a fluorescence microscopy with the Fura-2 loading method. S1P produced a concentration-dependent increase in [Ca2+]i in the cells. Pretreatment with EGTA, an extracellular Ca2+ chelator, decreased the S1P-induced increase in [Ca2+]i, and an L-type Ca2+-channel blocker, nimodipine, decreased the effect of S1P. This indicates that Ca2+ influx may be required for muscle contraction by S1P. When stimulated with thapsigargin, an intracellular calcium chelator, or 2-Aminoethoxydiphenyl borate (2-APB), an InsP3 receptor blocker, the S1P-evoked increase in [Ca2+]i was significantly decreased. Treatment with pertussis toxin (PTX), an inhibitor of Gi-protein, suppressed the increase in [Ca2+]i evoked by S1P. These results suggest that the S1P-induced increase in [Ca2+]i in cat esophageal smooth muscle cells occurs upon the activation of phospholipase C and subsequent release of Ca2+ from the InsP3-sensitive Ca2+ pool in the sarcoplasmic reticulum. These results suggest that S1P utilized extracellular Ca2+ via the L type Ca2+ channel, which was dependent on activation of the S1P4 receptor coupled to PTX-sensitive Gi protein, via phospholipase C-mediated Ca2+ release from the InsP3-sensitive Ca2+ pool in cat esophageal smooth muscle cells.
Keywords: Sphingosine-1-phosphate, Calcium, Fura-2, Esophageal cells, 2-Aminoethoxydiphenyl borate, Nimodipine

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