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. 2020 Mar 28;26(12):1242–1261. doi: 10.3748/wjg.v26.i12.1242

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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

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The main signaling pathways of G protein-coupled receptors. A: Proton-sensing G protein-coupled receptors and G protein-coupled receptor 55 are coupled to G13 proteins and are involved in G13/Rho signaling pathways, mediating the modulation of cytoskeleton formation and cell adhesion; B: Proton-sensing G protein-coupled receptors, G protein-coupled receptor 30 and β-adrenergic receptors are implicated in Gs/adenylyl cyclase/cyclic adenosine monophosphate (cAMP) signaling pathways and multiple phosphorylation events, and then mediate immunoregulation, inflammatory responses and autophagy. In addition, G protein-coupled receptor 4 is also implicated in cAMP/exchange protein activated by cAMP (Epac) signaling pathways, and then affects cell adhesion; C: G protein-coupled receptor 4, G protein-coupled receptor 68, G protein-coupled receptor 132, G protein-coupled receptor 55, type 1 muscarinic receptor and type 3 muscarinic receptor bind to Gq proteins and are involved in Gq/phospholipase C/Ca²⁺ signaling pathways, then phosphorylate target proteins, mediating the regulation of immune response, inflammatory reaction and autophagy; D: Cannabinoid receptor 1 and cannabinoid receptor 2 are coupled to Gi proteins and are involved in immunoregulation, inflammatory responses and autophagy through Gi/adenylyl cyclase/cAMP and Gi/phosphatidylinositol 3 kinase/Akt signaling pathways. GPCRs: G protein-coupled receptors; GPR55: G protein-coupled receptor 55; ROCK: Rho associated coiled-coil containing protein kinase; GPR30: G protein-coupled receptor 30; β-ARs: β-adrenergic receptors, including β1-, β2- and β3-adrenergic receptor; AC: Adenylyl cyclase; cAMP: Cyclic adenosine monophosphate; GPR4: G protein-coupled receptor 4; Epac: Exchange protein activated by cAMP; Rap1: Ras associated protein 1; PKA: Protein kinase A; GPR68: G protein-coupled receptor 68; GPR 132: G protein-coupled receptor 132; M1R: Type 1 muscarinic receptor; M3R: Type 3 muscarinic receptor; PLC: Phospholipase C; PIP2: Phosphatidylinositol 4,5-bisphosphate; IP3: Inositol 1,4,5-triphosphate; DG: Diacylglycerol; PKC: Protein kinase C; CB1: Cannabinoid receptor 1; CB2: Cannabinoid receptor 2; PI3K: Phosphatidylinositol 3 kinase; Akt: Also known as protein kinase B (PKB); Proton-sensing GPCRs: GPR4, GPR68, GPR65 and GPR132; Phosphorylation: nuclear factor kappa-B (NF-kB), extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (p38MAPK) etc.