GPR119

GPR119 is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents.^[9] Activation of the receptor has been shown to cause a reduction in food intake and body weight gain in rats.^[9] GPR119 has also been shown to regulate incretin and insulin hormone secretion.^[10][11][12] As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes.^[9][11][13]

A number of endogenous, synthetic and plant derived ligands for this receptor have been identified:^[14][15][16]

• 2-Oleoylglycerol (2OG)^[17]
• Anandamide^[13]
• AR-231,453^[18]
• MBX-2982^[19]
• Oleoylethanolamide (OEA)^[6][9][13] (Endogenous Ligand) ^[6]
• PSN-375,963^[9][10]
• PSN-632,408^[9][10]

Commensal bacteria are found to have important roles in human health, as bacterial metabolites are likely to be key components of host interactions by which they affect mammalian physiology.^[20] N-acyl amide synthase genes are found enriched in gastrointestinal bacteria and the lipids, that they encode, interact with GPCRs, which regulate gastrointestinal tract physiology, where cell-based models have demonstrated, that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, and the clearest overlap in structure and function between bacterial and human GPCR-active ligands, is found for the endocannabinoid receptor GPR119.^[21]

The experiment have isolated both the palmitoyl and oleoyl analogs of N-acyl serinol, and found the latter only differs from 2-OG: C₂₁H₄₀O₄ by the presence of an amide instead of an ester, and from OEA: C₂₀H₃₉NO₂ by the presence of an additional ethanol substituent, where the N-oleoyl serinol (C₂₁H₄₁NO₃; 18:1,n-9),^[22] is a similarly potent GPR119 agonist compared to the endogenous ligand OEA (EC50 12 μM vs. 7 μM), but elicits almost a 2-fold greater maximum activation, do suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria,^[21] that communicate through interactions between these two fundamental systems—which form the gut microbiota-endocannabinoidome axis.^[20]

Paralogues edit

Source:^[23]

• GPR6
• MC5R
• MC3R
• MC4R
• CNR1
• GPR12
• S1PR1
• MC1R
• S1PR3
• S1PR5
• GPR3
• S1PR2
• CNR2
• LPAR3
• LPAR1
• LPAR2
• MC2R
• S1PR4