Table 1.
Role of P2 and P1 receptors in neuroinflammation and experimental encephalomyelitis
| Receptor | Natural agonist(s) | Expression in the CNS | Demonstrated and/or potential role in the CNS | Role in experimental encephalomyelitis (EAE) |
|---|---|---|---|---|
| P2X7 | ATP (mM) | Microglia astrocytes oligodendroglia Schwann cells leukocytes and ↑immunoreactivity in neurons and astrocytes of MS patients | Induces IL-1β maturation and release | P2X7 stimulation causes lesions resembling MS plaques |
| Regulates microglia proliferation and apoptosis | Significantly reduced severity of EAE either in P2X7 knockout mice or in wild-type mice treated with P2X7 antagonists | |||
| Triggers superoxide generation and ATP release by microglia | ||||
| P2Y2 | ATP and UTP | Neurons, microglia, astrocytes, and leukocytes | Controls migration of glial cells and leukocytes | ND |
| Triggers the release of chemokines IL-8 and MCP-1 | ||||
| P2Y6 | UDP | Microglia, leukocytes, and blood vessel cells | Controls leukocyte recruitment via IL-8 production | ND |
| Controls microglia phagocytosis | ||||
| P2Y11 | ATP and ADP | Leukocytes | Involved in neutrophil chemotaxis and apoptosis | ND |
| Controls key immune responses of dendritic cells | ||||
| P2Y12 | ADP | Oligodendrocytes, microglia, and astrocytes | Involved in myelination | ND |
| GPR17 | UDP, UDP glucose, and cysteinyl leukotrienes | Neurons, parenchymal, oligodendrocyte, and precursor cells | Involved in neurodegeneration and remodeling/repair processes following brain injury | ND |
| A1 | Adenosine | Neurons, microglia, astrocytes, leukocytes (except for T lymphocytes), and ↓expression in MS patients | Protects against neuroinflammation and demyelination in patients with MS and allergic EAE | A1 knockout mice display increased neuroinflammation and demyelination |
| Promotes tissue repair via stimulation of neuronal growth factor release from astrocytes | ||||
| A2A and A2B | Adenosine | Neurons, microglia (except for A2B), astrocytes, and leukocyte | A2A knockout mice display an increased production of proinflammatory cytokines | ND |
| Antagonize T cell receptor signalling and IL-2 release | ||||
| A3 | Adenosine | Neurons, microglia, astrocytes, and leukocytes | Induces the release of IL-6 and CCL2 from astrocytes | ND |
| Decreases LPS-induced TNF-α production by microglia and NK activation |
ND not determined