Reactivation of Gαi-coupled formyl peptide receptors is inhibited by Gαq-selective inhibitors when induced by signals generated by the platelet-activating factor receptor

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Kö¹  Kostenis, Evi¹  Gabl, Michael²  Dahlstrand Rudin, Agnes³  Rajabkhani, Zahra⁴  nig, Gabriele M.⁴  Forsman, Huamei⁵  Dahlgren, Claes⁵ 

[1] and;Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden;Molecular, Cellular and Pharmacobiology Section, Institute of Pharmaceutical Biology, University of Bonn, Bonn, Germany

关键词: neutrophil;    receptor crosstalk;    signal transduction;    priming;    NADPH‐;    oxidase;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Formyl peptide receptor (FPR)–desensitized neutrophils display increased production/release of superoxide (O₂⁻) when activated by platelet-activating factor (PAF), a priming of the response achieved through a unique receptor crosstalk mechanism. The aim of this study was to determine the effect of an inhibitor selective for small, heterotrimeric G proteins belonging to the Gαq subclass on that receptor crosstalk. We show that signals generated by FPRs and the PAF receptor (PAFR) induce activation of the neutrophil O₂⁻, producing NADPH-oxidase, and that response was sensitive to Gαq inhibition in cells activated by PAF, but no inhibition was obtained in cells activated by FPR agonists. Signaling in naive neutrophils is terminated fairly rapidly, and the receptors become homologously desensitized. The downstream sensitivity to Gαq inhibition in desensitized cells displaying increased production/release of O₂⁻ through the PAFR receptor crosstalk mechanism also comprised the reactivation of the FPRs, and the activation signals were redirected from the PAFR to the desensitized/reactivated FPRs. The Gαq-dependent activation signals generated by the PAFRs activate the Gαi-coupled FPRs, a receptor crosstalk that represents a novel pathway by which G protein-coupled receptors can be regulated and signaling can be turned on and off.

【 授权许可】

CC BY