Photolysis of intracellular caged sphingosine‐1‐phosphate causes Ca2+ mobilization independently of G‐protein‐coupled receptors

FEBS Letters

Jakobs, Karl H.¹  Jaggar, Jonathan H.³  Schaefer, Michael⁴  Meyer zu Heringdorf, Dagmar¹  Danneberg, Kerstin¹  Liliom, Karoly²  Tigyi, Gabor³ 

[1] Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany;Institute of Enzymology, Hungarian Academy of Sciences, H-1518 Budapest, Hungary;Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA;Institut für Pharmakologie, Freie Universität Berlin, D-14195 Berlin, Germany

关键词: Ca2+ mobilization;    Photolysis;    Sphingosine-1-phosphate;    Thapsigargin-sensitive Ca2+ store;    [Ca2+]i;    cytosolic free Ca2+ concentration;    GPCR;    G-protein-coupled receptor;    HBSS;    Hank's balanced salt solution;    I Cl;    chloride current;    IP3;    inositol-1;    4;    5-trisphosphate;    PTX;    pertussis toxin;    S1P;    sphingosine-1-phosphate;   

DOI  :  10.1016/S0014-5793(03)01219-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Sphingosine-1-phosphate (S1P), the product of sphingosine kinase, activates several widely expressed G-protein-coupled receptors (GPCR). S1P might also play a role as second messenger, but this hypothesis has been challenged by recent findings. Here we demonstrate that intracellular S1P can mobilize Ca²⁺ in intact cells independently of S1P-GPCR. Within seconds, S1P generated by the photolysis of caged S1P raised the intracellular free Ca²⁺ concentration in HEK-293, SKNMC and HepG2 cells, in which the response to extracellularly applied S1P was either blocked or absent. Ca²⁺ transients induced by photolysis of caged S1P were caused by Ca²⁺ mobilization from thapsigargin-sensitive stores. These results provide direct evidence for a true intracellular action of S1P.

【 授权许可】

Unknown