Photolysis of intracellular caged sphingosine-1-phosphate causes Ca2+ mobilization independently of G-protein-coupled receptors.
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 Ca(2+) in intact cells independently of S1P-GPCR. Within seconds, S1P generated by the photolysis of caged S1P raised the intracellular free Ca(2+) concentration in HEK-293, SKNMC and HepG2 cells, in which the response to extracellularly applied S1P was either blocked or absent. Ca(2+) transients induced by photolysis of caged S1P were caused by Ca(2+) mobilization from thapsigargin-sensitive stores. These results provide direct evidence for a true intracellular action of S1P.
Meyer zu Heringdorf
Dagmar
D
Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany. meyer-heringdorf@uni-essen.de
Liliom
Karoly
K
Schaefer
Michael
M
Danneberg
Kerstin
K
Jaggar
Jonathan H
JH
Tigyi
Gabor
G
Jakobs
Karl H
KH
D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry*; D008246:Lysophospholipids; D008856:Microscopy, Fluorescence / Q000379:methods; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism*; D010782:Photolysis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology
D008246:Lysophospholipids; D010755:Organophosphates; D043562:Receptors, G-Protein-Coupled; C116619:caged sphingosine 1-phosphate; C060506:sphingosine 1-phosphate; D019284:Thapsigargin; D013110:Sphingosine; D002118:Calcium