Table 2.
G-protein coupling, physiological ligands, tissue distribution, and effects of muscarinic acetylcholine receptor subtype activation in health and disease.
| MR Subtype (Gene) |
G-Protein | Ligands | Tissue Distribution | Physiological Actions | Actions in GI Cancers | Refs. |
|---|---|---|---|---|---|---|
| M1R (CHRM1) |
Gq/11 | ACh, BA, cholesterol (allosteric) | Brain, gastric mucosa, respiratory epithelium, skin, melanocytes, immunocytes | Mediates gastric pepsinogen secretion | Protects against PDAC and colon neoplasia | [34,40,41,50,51,52,53] |
| M2R (CHRM2) |
Gi/o | ACh | Brain, heart, ENS, gastric mucosa, skin, bladder, melanocytes, smooth muscle, immunocytes | Modulates cardiac rhythm, GI motility | None reported | [34,50,53,54,55,56] |
| M3R (CHRM3) |
Gq/11 | ACh, BA | Gastric chief and parietal cells, colon epithelial cells, smooth muscle, ENS, brain, skin, melanocytes, immunocytes | Mediates gastric acid and pepsinogen secretion; GI motility | Promotes gastric and colon cancer cell proliferation and PDAC severity | [37,38,50,52,57,58,59,60,61,62] |
| M4R (CHRM4) |
Gi/o | ACh | Brain, gastric mucosa, small intestine, skin, melanocytes, immunocytes | Enhances gastric acid secretion; regulates striatal dopamine release | None reported | [34,50,57,63,64] |
| M5R (CHRM5) |
Gq/11 | ACh | Brain, cerebral vasculature, ENS; mRNA expressed in testes, placenta, thyroid, small intestine, immunocytes | Enhances gastric acid secretion; regulates striatal dopamine release; mediates SNc excitability | None reported | [34,50,53,61,63,65,66] |
Refs, references; MR, muscarinic receptor; ACh, acetylcholine; BA, bile acids; ENS, enteric nervous system; GI, gastrointestinal; PDAC, pancreatic ductal adenocarcinoma; SNc, substantia nigra pars compacta.