PMID- 10383399
OWN - NLM
STAT- MEDLINE
DCOM- 19990727
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 27
DP  - 1999 Jul 2
TI  - Differential pharmacological properties and signal transduction of the
      sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.
PG  - 18997-9002
AB  - Sphingosine 1-phosphate (SPP) is a potent lipid mediator released upon cellular
      activation. In this report, pharmacological properties of the three
      G-protein-coupled receptors (GPCRs) for SPP, EDG-1, -3, and -5 are characterized 
      using a Xenopus oocyte expression system, which lacks endogenous SPP receptors.
      Microinjection of the EDG-3 and EDG-5 but not EDG-1 mRNA conferred SPP-responsive
      intracellular calcium transients; however, the EDG-5 response was quantitatively 
      much less. Co-expression of EDG-1 receptor with the chimeric Galphaqi protein
      conferred SPP responsiveness. Galphaqi or Galphaq co-injection also potentiated
      the EDG-5 and EDG-3 mediated responses to SPP. These data suggest that SPP
      receptors couple differentially to the Gq and Gi pathway. All three GPCRs were
      also activated by sphingosylphosphorylcholine, albeit at higher concentrations.
      None of the other related sphingolipids tested stimulated or blocked SPP-induced 
      calcium responses. However, suramin, a polycyclic anionic compound, selectively
      antagonized SPP-activated calcium transients in EDG-3 expressing oocytes with an 
      IC50 of 22 microM, suggesting that it is an antagonist selective for the EDG-3
      GPCR isotype. We conclude that the three SPP receptors signal differentially by
      coupling to different G-proteins. Furthermore, because only EDG-3 was antagonized
      by suramin, variations in receptor structure may determine differences in
      antagonist selectivity. This property may be exploited to synthesize receptor
      subtype-specific antagonists.
FAU - Ancellin, N
AU  - Ancellin N
AD  - Center for Vascular Biology, Department of Physiology, University of Connecticut 
      Health Center, Farmington, Connecticut 06030-3505, USA.
FAU - Hla, T
AU  - Hla T
LA  - eng
GR  - DK45659/DK/NIDDK NIH HHS/United States
GR  - HL54710/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Lysophospholipid)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 50934-79-7 (Aequorin)
RN  - 6032D45BEM (Suramin)
SB  - IM
MH  - 3T3 Cells
MH  - Aequorin/metabolism
MH  - Animals
MH  - DNA-Binding Proteins/*physiology
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Immediate-Early Proteins/*physiology
MH  - Jurkat Cells
MH  - Mice
MH  - NF-KappaB Inhibitor alpha
MH  - Oocytes/metabolism
MH  - Rats
MH  - Receptors, Cell Surface/*physiology
MH  - *Receptors, G-Protein-Coupled
MH  - Receptors, Growth Factor/*physiology
MH  - Receptors, Lysophospholipid
MH  - *Signal Transduction
MH  - Suramin/pharmacology
MH  - Xenopus
EDAT- 1999/06/26 00:00
MHDA- 1999/06/26 00:01
CRDT- 1999/06/26 00:00
PHST- 1999/06/26 00:00 [pubmed]
PHST- 1999/06/26 00:01 [medline]
PHST- 1999/06/26 00:00 [entrez]
AID - 10.1074/jbc.274.27.18997 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 2;274(27):18997-9002. doi: 10.1074/jbc.274.27.18997.