ENDOCANNABINOID SIGNALING IN THE BODY
The two classical cannabinoid receptors, CB1 and CB2, are expressed by enteric neurons, immune cells, and other cell types within the gastrointestinal tract. The gut and the liver also synthesize two key ligands—anandamide (AEA) and 2-arachidonoylglycerol (2-AG)—for those receptors. Combined, this signaling system acts locally in the gut and liver, but also communicates with the brain to affect food intake, pain, inflammation, and more.
In the liver, endocannabinoids are thought to act almost like hormones, stimulating cell division at some times, cell death at others. In the healthy liver, expression of CB receptors is very low, but in a diseased liver expression increases, and endocannabinoid ligands are released from all four cell types shown here. Many ligands are produced and bind to CB1 receptors, causing lipid accumulation and insulin resistance in hepatocytes, and increased proliferation of activated stellate cells, the major cell type involved in fibrosis (scarring) of the liver. Blocking CB1 receptors with drugs decreased the amount of fibrosis in mouse models.
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