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Formyl Peptide Receptors in Mice and Men: Similarities and Differences in Recognition of Conventional Ligands and Modulating Lipopeptides
Author(s) -
Winther Malene,
Dahlgren Claes,
Forsman Huamei
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12903
Subject(s) - allosteric regulation , receptor , g protein coupled receptor , allosteric modulator , biology , computational biology , peptide , functional selectivity , drug development , inflammation , microbiology and biotechnology , drug , pharmacology , biochemistry , immunology
The pattern recognition formyl peptide receptors ( FPR s) belong to the class of G‐protein‐coupled receptors ( GPCR s), the largest group of cell surface receptors involved in a range of physiological processes and pathologies. The FPR s have regulatory function in the initiation as well as resolution of inflammatory reactions, making them highly interesting as targets for drug development. Recent research in the GPCR / FPR fields has uncovered novel receptor biology concepts, including biased signalling/functional selectivity, allosteric modulation, receptor reactivation and receptor cross‐talk. When it comes to allosteric modulators, ‘tailor‐made’ lipopeptides (pepducins and lipopeptoids) represent a novel concept of GPCR / FPR regulation. This MiniReview is focused on the basis for recognition of conventional ligands and immunomodulating lipopeptides, novel allosteric modulators for the FPR s, receptors that are highly expressed by both human and mouse neutrophils. The FPR s play key roles in host defence against microbial infections, tissue homeostasis and the initiation as well as resolution of inflammation but there are both similarities and differences in ligand recognition between mice and men. Thus, identification and functional characterization of activating and inhibiting ligands should provide insights into future design of FPR ‐based animal models of human diseases and development of therapeutics for treating inflammatory diseases.