Activation of the human FPRL-1 receptor promotes Ca2+ mobilization in U87 astrocytoma cells.
The human formyl peptide receptor like 1 (FPRL-1) is a variant of the Gi-coupled formyl-peptide receptor. Functional FPRL-1 is endogenously expressed in the U87 astrocytoma cell line and there is accumulating evidence to suggest that FPRL-1 may be involved in neuroinflammation associated with the pathogenesis of Alzheimer's disease. In this study, we examined the ability of FPRL-1 to mobilize intracellular Ca2+ in U87 astrocytoma cells, as well as in Chinese hamster ovary (CHO) cells stably expressing FPRL-1. We showed that Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM), a specific agonist for FPRL-1, stimulated Ca2+ influx in both U87 and FPRL-1/CHO cells. These effects can be inhibited by the FPRL-1 selective antagonist, WRW4. Involvement of Gi proteins was demonstrated with the use of pertussis toxin, while inhibitors of store-operated channels (SOC) including 1-[2-(4-methoxyphenyl)]-2-[3-(4-methpxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride (SKF96365) and 2-aminoethoxydiphenyl borate (2-APB) were found to abolish the WKYMVM-induced Ca2+ increase. However, intracellular Ca2+ mobilization in both cell lines were unaffected by the phospholipase Cbeta inhibitor U73122 or selective ryanodine receptor inhibitors. Our data demonstrated that activation of Gi-coupled FPRL-1 can lead to Ca2+ influx possibly via SOCs in U87 and FPRL-1/CHO cells.
Kwan
Dawna H T
DH
Department of Biochemistry, The Molecular Neuroscience Center, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Kam
Angel Y F
AY
Wong
Yung H
YH
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D001483:Base Sequence; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D006801:Humans; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D002118:Calcium
Cell Calcium. 2005 Sep-Oct;38(3-4):375-82
16105683
FASEB J. 2002 Aug;16(10 ):1145-50
12153982
J Neuroimmunol. 2000 Nov 1;111(1-2):102-8
11063827
Brain Res. 1997 May 30;758(1-2):69-82
9203535
J Physiol. 2001 Oct 1;536(Pt 1):3-19
11579153
Neuroscience. 2006;137(4):1347-58
16343781
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2941-4
12601149
J Cell Sci. 2001 Jun;114(Pt 12):2223-9
11493662
Biochemistry. 1997 May 27;36(21):6415-23
9174358
Infect Immun. 2002 Jun;70(6):2908-14
12010979
J Immunol. 2001 Feb 1;166(3):1448-51
11160182
Science. 2000 Mar 3;287(5458):1647-51
10698739
Eur J Neurosci. 1999 Feb;11(2):383-8
10051738
Assay Drug Dev Technol. 2004 Jun;2(3):269-80
15285908
Clin Biochem. 1998 Apr;31(3):137-41
9629486
Neurobiol Aging. 2005 Mar;26(3):349-54
15639313
FEBS Lett. 1990 Apr 9;263(1):5-9
2185036
J Neurochem. 2006 Apr;97(1):245-54
16524374
J Immunol. 2003 Dec 15;171(12):6807-13
14662886
Physiol Rev. 2005 Apr;85(2):757-810
15788710
J Neurosci. 1998 Sep 1;18(17):6822-9
9712653
J Biochem. 1997 Sep;122(3):498-505
9348075
J Immunol. 2004 Jul 1;173(1):607-14
15210823
Eur J Neurosci. 2003 Oct;18(8):2133-45
14622174
Blood. 2003 Feb 15;101(4):1572-81
12393391
Nat Med. 2001 Nov;7(11):1209-16
11689885
Physiol Rev. 2000 Oct;80(4):1291-335
11015615
Br J Pharmacol. 2004 May;142(1):150-60
15037513
Trends Neurosci. 1994 Dec;17(12):531-6
7532338
Nature. 1994 Jun 30;369(6483):744-7
7911978
J Leukoc Biol. 2002 Oct;72(4):628-35
12377930
Biochem Soc Trans. 2003 Oct;31(Pt 5):925-9
14505450
J Immunol. 2002 Apr 15;168(8):4063-9
11937565
J Biol Chem. 2001 Jun 15;276(24):21585-93
11285256
Cytokine Growth Factor Rev. 2001 Mar;12(1):91-105
11312121
Biochim Biophys Acta. 2004 Dec 6;1742(1-3):9-20
15590052
Biosci Rep. 1996 Apr;16(2):139-57
8790919
J Exp Med. 1999 Jan 18;189(2):395-402
9892621
J Biol Chem. 1997 Nov 21;272(47):29672-80
9368034
J Immunol. 1995 Oct 15;155(8):4004-10
7561109
J Immunol. 1997 Feb 15;158(4):1895-901
9029131
J Biol Chem. 1992 Apr 15;267(11):7637-43
1373134
J Exp Med. 2000 Oct 2;192(7):1069-74
11015447
Cell. 1999 Aug 20;98 (4):487-99
10481913
Biochem J. 2001 Mar 1;354(Pt 2):285-90
11171105
J Biol Chem. 2001 Jun 1;276(22):18888-96
11259416
Br J Pharmacol. 1997 Mar;120(6):1165-71
9134231
Nat Neurosci. 2001 Aug;4(8):803-12
11477426
Mol Pharmacol. 2000 Apr;57(4):700-8
10727515
J Neurosci. 2001 Jan 15;21(2):RC123
11160457
Glia. 2003 Mar;41(4):347-53
12555202
J Leukoc Biol. 2001 Jul;70(1):155-61
11435499
J Exp Med. 1994 Jul 1;180(1):253-60
8006586
Trends Immunol. 2002 Nov;23(11):541-8
12401407
Biochem Biophys Res Commun. 1992 Apr 30;184(2):582-9
1374236