Review
Copyright ©The Author(s) 2020.
World J Gastroenterol. Mar 28, 2020; 26(12): 1242-1261
Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1242
Table 1 Roles of G protein-coupled receptors in inflammatory bowel disease and the main signaling pathways of G protein-coupled receptors
GPCRsMain signaling pathwaysRoles
Proton-sensing GPCRs
GPR4Gs/AC/cAMP, cAMP/Epac, Gq/PLC/Ca2+, G13/Rho and NF-κB signaling pathwaysPromotes leukocyte adhesion and increases the expression levels of adhesion molecules and inflammatory genes
GPR68Gs/AC/cAMP, Gq/PLC/Ca2+, G13/Rho and ERK/p38MAPK signaling pathwaysAggravates intestinal inflammation and fibrogenesis, and improves epithelial barrier function
GPR65Gs/AC/cAMP and G13/Rho signaling pathwaysAlleviates inflammatory responses, and maintains epithelial barrier and lysosome function
GPR132Gs/AC/cAMP, Gq/PLC/Ca2+, G13/Rho, Ras/ERK signaling pathwaysShows bidirectional effects on inflammation and controls the polarization of macrophages
Cannabinoid receptors
CB1 and CB2Gi/AC/cAMP, Gi/PI3K/Akt and ERK/p38MAPK signaling pathwaysInhibit intestinal motility, secretion and inflammation; increase susceptibility to IBD; and affect the course of the disease
GPR55Gq/PLC/Ca2+ and G13/Rho signaling pathwaysRegulates intestinal motility and neuropathic and inflammatory pain, and shows bidirectional effects on intestinal inflammation
Autonomic nervous system GPCRs
M1R and M3RGq/PLC/Ca2+, ERK/p38MAPK and NF-κB signaling pathwaysShow bidirectional effects on intestinal secretion and inflammation, and maintain epithelial barrier
β-ARsGs/AC/cAMP signaling pathwaysAlleviate inflammatory responses
Estrogen related GPCRs
GPR30Gs/AC/cAMP, PI3K/Akt and Src/ERK signaling pathwaysAlleviates 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.