title: A distinct G(i) protein-coupled receptor for sphingosylphosphorylcholine in human leukemia HL-60 cells and human neutrophils.
abstract: 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.
authors.affiliation: Institut für Pharmakologie, Universität GH Essen, Germany. van_koppen@uni-essen.de
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Koppen
authors.forename: D
authors.initials: D
authors.lastname: Meyer Zu Heringdorf
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: K T
authors.initials: KT
authors.lastname: Laser
authors.forename: K H
authors.initials: KH
authors.lastname: Jakobs
mesh_terms: 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
chemical_list: 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