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Activation of the Human FPRL-1 Receptor Promotes Ca2+ Mobilization in U87 Astrocytoma Cells

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Abstract

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 Cβ 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.

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Abbreviations

2-APB:

2-Aminoethoxydiphenyl borate

cADPR:

Cyclic ADP-ribose

fMLP:

N-Formyl peptide

FPR:

Formyl peptide receptor

FPRL-1:

Formyl peptide receptor like 1

PTX:

Pertussis toxin

SAA:

Serum amyloid A

SOC:

Store-operated channel

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Acknowledgments

We are grateful to Dr. Richard Ye for kindly providing the cDNA of FPRL-1 and Dr. Andrew Miller for kindly providing the GdCl3. We also thank Dr. David New for generating the FPRL-1/CHO cells. This work was supported in part by grants from the Research Grants Council of Hong Kong (HKUST 3/03C), the University Grants Committee (AoE/B-15/01), and the Hong Kong Jockey Club. YHW was a recipient of the Croucher Senior Research Fellowship.

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  1. Angel Y. F. Kam

    Present address: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

Authors and Affiliations

  1. 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

    Dawna H. T. Kwan, Angel Y. F. Kam & Yung H. Wong

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  1. Dawna H. T. Kwan
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  2. Angel Y. F. Kam
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Correspondence to Yung H. Wong.

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Kwan, D.H.T., Kam, A.Y.F. & Wong, Y.H. Activation of the Human FPRL-1 Receptor Promotes Ca2+ Mobilization in U87 Astrocytoma Cells. Neurochem Res 33, 125–133 (2008). https://doi.org/10.1007/s11064-007-9425-7

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