A distinct G(i) protein-coupled receptor for sphingosylphosphorylcholine in human leukemia HL-60 cells and human neutrophils.
The sphingolipids, sphingosylphosphorylcholine (SPPC) and sphingosine-1-phosphate (SPP), induce a rapid and transient rise in intracellular free calcium concentration ([Ca2+]i) in a variety of cell lines via activation of pertussis toxin-sensitive G protein-coupled receptors. We investigated whether these sphingolipids act on different receptors by testing the effect of varying concentrations of SPPC on [Ca2+]i in human leukemia HL-60 cells, which have been found to be nonresponsive to SPP. SPPC potently (EC50 = 1.5 microM) and rapidly increased [Ca2+]i in HL-60 cells in a pertussis toxin-sensitive manner. Differentiation of HL-60 cells through treatment with dibutyryl cAMP into granulocyte-like cells did not change the magnitude or the pertussis toxin sensitivity of the SPPC-induced [Ca2+]i rise, indicating that the receptor for SPPC is constitutively expressed in HL-60 cells. SPPC did not activate phospholipase C or D in HL-60 cells. However, SPPC, but not SPP, stimulated the generation of superoxide anions in dibutyryl cAMP-differentiated HL-60 cells as well as in human neutrophils, suggesting that the SPPC receptor may play a role in the inflammatory defense against invading microorganisms. On the basis of these results, we conclude that there apparently is a heterogeneity of G protein-coupled receptors for sphingolipids in mammalian cells.
Van Koppen
C J
CJ
Institut für Pharmakologie, Universität GH Essen, Germany. van_koppen@uni-essen.de
Meyer Zu Heringdorf
D
D
Zhang
C
C
Laser
K T
KT
Jakobs
K H
KH
D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D008246:Lysophospholipids; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D008246:Lysophospholipids; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013481:Superoxides; C060506:sphingosine 1-phosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010738:Type C Phospholipases; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D013110:Sphingosine; D002118:Calcium