Table 5 —
GPCRs that are potential targets for pharmacotherapy in sepsis
| Endogenous target | Pharmacothe rapy | Anticipated effects |
|---|---|---|
| Adenosine receptors | A2A receptor blockade | Immune stimulation and mitigation of inflammation |
| A3 receptor activation | ||
| Adrenoceptors | β-adrenoceptor stimulation | Modification of cytokine expression profile of immune cells |
| Complement receptors | C3aR1 modulation | Re-establishment of vascular endothelial barrier |
| C5aR1 modulation | ||
| Chemokine receptors | ACKR2 activation | Blockade of cytokine storm during hyper-inflammatory phase of sepsis |
| CCR2 blockade | ||
| CCR5 activation | ||
| CX3CR1 stimulation | ||
| Coagulation cascade | PAR1 modulation | Restoration of physiologic endothelial function |
| Cannabinoid receptors | CB1 and CB2 receptor modulation | Alleviation of sepsis-induced multi-organ dysfunction |
| Endothelin receptors | ETA receptor blockade and ETB1 receptor stimulation | Restoration of mitochondrial oxidative phosphorylation and alleviation of sepsis-induced hypoperfusion |
| LPI receptor | LPI1 receptor blockade | Reconstitution of the blood-gut barrier |
| Sphingosine-1-phosphate | S1P1 receptor stimulation | Re-establishment of vascular endothelial barrier |
| Melatonin receptors | MT1 and MT2 receptor stimulation | Normalization of pineal gland-immune axis |
| Resolvin receptors | FPR2 and DRV2 receptor stimulation | Enhancing bacterial clearance and promoting resolution of inflammation |
| Ghrelin receptor | GHS-R stimulation | Immune stimulation and mitigation of inflammation |
| Hydroxycarboxylic acid receptors | HCAR2 stimulation | Reconstitution of the blood-gut barrier and intestinal microbiome |
| Urotensin II receptors | Urotensin II receptor blockade | Alleviation of sepsis-induced multi-organ dysfunction |
ACKR2 = Atypical chemokine receptor 2; C3aR1 = complement protein 3a receptor 1; C5aR1 = complement protein 5a receptor 1; CB = cannabinoid; CCR = CC-chemokine receptor; CX3CR = CX3C chemokine receptor; DRV2 = D-series resolvin 2 receptor; ET = endothelin; FPR = formylpeptide receptor; GHS-R = growth hormone secretagogue receptor; GPCR = G protein-coupled receptor; HCAR = hydroxycarboxylic acid receptor; LPI = lysophosphatidylinositol; MT = melatonin; PAR = protease-activated receptor; S1P = sphingosine-1-phosphate.