Depolarisation induces rapid and transient formation of intracellular sphingosine‐1‐phosphate

FEBS Letters

Ruwisch, Lars³  Jakobs, Karl H.¹  Hashemi, Rozita¹  Alemany, Regina¹  Spiegel, Sarah²  Meyer zu Heringdorf, Dagmar¹  Kleuser, Burkhard³  Danneberg, Kerstin¹  Lass, Holger¹ 

[1] Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany;Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA;Institut für Pharmazie, Freie Universität Berlin, D-14195 Berlin, Germany

关键词: Sphingosine kinase;    Sphingosine-1-phosphate;    KCl depolarisation;    Bradykinin;    Noradrenaline release;    PC12 cell;    BSA;    bovine serum albumin;    [Ca2+]i;    cytosolic free Ca2+ concentration;    DMS;    N;    N-dimethylsphingosine;    GPCR;    G-protein-coupled receptor;    HBSS;    Hanks’ balanced salt solution;    PKC;    protein kinase C;    SPK1;    sphingosine kinase-1;    SPP;    sphingosine-1-phosphate;    tDHS;    DL-threo-dihydrosphingosine;   

DOI  :  10.1016/S0014-5793(01)03168-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Formation of sphingosine-1-phosphate (SPP) by sphingosine kinase serves as a signalling pathway for various membrane receptors. Here, we show that membrane depolarisation is another mechanism by which this pathway can be activated. Formation of [³H]SPP as well as levels of endogenous SPP were rapidly and transiently increased in PC12 pheochromocytoma cells depolarised with high KCl. Time course and maximum were similar to those induced by bradykinin. Depolarisation-induced SPP production was also observed in RINm5F insulinoma cells, dependent on extracellular Ca²⁺ and fully suppressed by verapamil, thus apparently caused by Ca²⁺ influx via voltage-gated Ca²⁺ channels. Studies with sphingosine kinase inhibitors and overexpression of sphingosine kinase revealed a partial contribution of this pathway to depolarisation-induced noradrenaline release and Ca²⁺ increase.

【 授权许可】

Unknown