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G protein-coupled receptors in rheumatology

Nature Reviews Rheumatology volume 10, pages 429–436 (2014)Cite this article

Subjects

Key Points

  • G protein-coupled receptors (GPCRs) are transmembrane receptor proteins involved in many pathophysiological processes in rheumatic diseases

  • GPCRs include a wide variety of receptors relevant to arthritis pathophysiology, including adenosine, chemokines, kinin B2, complement factor, and protease-activated receptors

  • Methotrexate, the most commonly used drug to treat rheumatoid arthritis, works via the adenosine A2A GPCR signalling pathway

  • Therapeutic approaches that target GPCRs could help in reducing the disease progression of a number of rheumatic diseases

Abstract

G protein-coupled receptors (GPCRs) are transmembrane receptor proteins that allow the transfer of signals across the cell membrane. In addition to their physiological role, GPCRs are involved in many pathophysiological processes including pathways relevant in rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis. Two-thirds of all currently available drugs target GPCRs directly or indirectly. However, the detailed mechanism of GPCR signalling is still unclear. Selective modification of GPCR-dependent signalling cascades to inhibit disease progression in rheumatic diseases is now being investigated. One approach is to use antibodies against ligands activating GPCRs. However, several GPCRs are known to be activated by only one ligand. In this case, targeting the receptor itself is a promising approach. So far, more information is available on GPCR action in RA as compared with OA, and even less information is available for other rheumatic diseases. Additional research on the role of GPCRs involved in the pathophysiology of rheumatic diseases is required to develop specific therapeutic approaches.

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Figure 1: Schematic diagram showing the structure of illustrative GPCRs known to have a role in rheumatic disease.
Figure 2: Schematic diagram of a GPCR with seven TM domains (TM1–TM7), extracellular loops (EL1–EL3) and intracellular loops (ICL1–ICL3).
Figure 3: Schematic diagram of GPCR signalling mediated by the activation of the G protein α subunit.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine and Rheumatology, Justus-Liebig University of Giessen, Rheumatology and Clinical Immunology, Kerckhoff Klinik, GmbH, Benekestrasse 2–8, Bad Nauheim, D-61231, Germany

    Elena Neumann, Kiran Khawaja & Ulf Müller-Ladner

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Contributions

E.N., K.K. and U.M.-L. contributed equally to researching data for article, substantial contribution to discussion of content, writing and review/editing of the manuscript before submission.

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Correspondence to Ulf Müller-Ladner.

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Neumann, E., Khawaja, K. & Müller-Ladner, U. G protein-coupled receptors in rheumatology. Nat Rev Rheumatol 10, 429–436 (2014). https://doi.org/10.1038/nrrheum.2014.62

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