Table 1.
Roles of G protein-coupled receptors in inflammatory bowel disease and the main signaling pathways of G protein-coupled receptors
| GPCRs | Main signaling pathways | Roles |
| Proton-sensing GPCRs | ||
| GPR4 | Gs/AC/cAMP, cAMP/Epac, Gq/PLC/Ca2+, G13/Rho and NF-κB signaling pathways | Promotes leukocyte adhesion and increases the expression levels of adhesion molecules and inflammatory genes |
| GPR68 | Gs/AC/cAMP, Gq/PLC/Ca2+, G13/Rho and ERK/p38MAPK signaling pathways | Aggravates intestinal inflammation and fibrogenesis, and improves epithelial barrier function |
| GPR65 | Gs/AC/cAMP and G13/Rho signaling pathways | Alleviates inflammatory responses, and maintains epithelial barrier and lysosome function |
| GPR132 | Gs/AC/cAMP, Gq/PLC/Ca2+, G13/Rho, Ras/ERK signaling pathways | Shows bidirectional effects on inflammation and controls the polarization of macrophages |
| Cannabinoid receptors | ||
| CB1 and CB2 | Gi/AC/cAMP, Gi/PI3K/Akt and ERK/p38MAPK signaling pathways | Inhibit intestinal motility, secretion and inflammation; increase susceptibility to IBD; and affect the course of the disease |
| GPR55 | Gq/PLC/Ca2+ and G13/Rho signaling pathways | Regulates intestinal motility and neuropathic and inflammatory pain, and shows bidirectional effects on intestinal inflammation |
| Autonomic nervous system GPCRs | ||
| M1R and M3R | Gq/PLC/Ca2+, ERK/p38MAPK and NF-κB signaling pathways | Show bidirectional effects on intestinal secretion and inflammation, and maintain epithelial barrier |
| β-ARs | Gs/AC/cAMP signaling pathways | Alleviate inflammatory responses |
| Estrogen related GPCRs | ||
| GPR30 | Gs/AC/cAMP, PI3K/Akt and Src/ERK signaling pathways | Alleviates inflammatory responses |
GPCRs: G protein-coupled receptors; GPR4: G protein-coupled receptor 4; AC: Adenylyl cyclase; cAMP: Cyclic adenosine monophosphate; Epac: Exchange protein activated by cAMP; PLC: Phospholipase C; NF-kB: Nuclear factor kappa-B; GPR68: G protein-coupled receptor 68; ERK: Extracellular signal-regulated kinase; p38MAPK: p38 mitogen-activated protein kinase; GPR65: G protein-coupled receptor 65; GPR132: G protein-coupled receptor 132; CB1: Cannabinoid receptor 1; CB2: Cannabinoid receptor 2; PI3K: Phosphatidylinositol 3 kinase; Akt: Also known as protein kinase B (PKB); GPR55: G protein-coupled receptor 55; M1R: Type 1 muscarinic receptor; M3R: Type 3 muscarinic receptor; β-ARs: β-adrenergic receptors; GPR30: G protein-coupled receptor 30.