Purinergic receptor
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Purinergic receptors, also known as purinoceptors, are a family of
The term purinergic receptor was originally introduced to illustrate specific classes of membrane receptors that mediate relaxation of gut smooth muscle as a response to the release of ATP (P2 receptors) or adenosine (P1 receptors). P2 receptors have further been divided into five subclasses: P2X, P2Y, P2Z, P2U, and P2T. To distinguish P2 receptors further, the subclasses have been divided into families of metabotropic (P2Y, P2U, and P2T) and ionotropic receptors (P2X and P2Z).[4]
In 2014, the first purinergic receptor in plants, DORN1, was discovered.[5]
3 classes of purinergic receptors
Name | Activation | Class |
P1 receptors |
adenosine | G protein-coupled receptors |
P2Y receptors |
nucleotides | G protein-coupled receptors |
P2X receptors |
ATP | ligand-gated ion channel |
There are three known distinct classes of purinergic receptors, known as P1, P2X, and P2Y receptors. [What about P2Z,U,T?]
P2X receptors
P2X receptors are
P2Y and P1 receptors
Both of these metabotropic receptors are distinguished by their reactivity to specific activators. P1 receptors are preferentially activated by adenosine and P2Y receptors are preferentially more activated by ATP. P1 and P2Y receptors are known to be widely distributed in the brain, heart, kidneys, and adipose tissue. Xanthines (e.g. caffeine) specifically block adenosine receptors, and are known to induce a stimulating effect to one's behavior.[10]
Inhibitors
Inhibitors of purinergic receptors include
Effects on chronic pain
Data obtained from using P2 receptor-selective antagonists has produced evidence supporting ATP's ability to initiate and maintain chronic pain states after exposure to noxious stimuli. It is believed that ATP functions as a pronociceptive neurotransmitter, acting at specific P2X and P2Y receptors in a systemized manner, which ultimately (as a response to noxious stimuli) serve to initiate and sustain heightened states of neuronal excitability. This recent knowledge of purinergic receptors' effects on chronic pain provide promise in discovering a drug that specifically targets individual P2 receptor subtypes. While some P2 receptor-selective compounds have proven useful in preclinical trials, more research is required to understand the potential viability of P2 receptor antagonists for pain.[11]
Recent research has identified a role for microglial P2X receptors in neuropathic pain and inflammatory pain, especially the P2X4 and P2X7 receptors.[12][13][14][15][16]
Effects on cytotoxic edema
Purinergic receptors have been suggested to play a role in the treatment of cytotoxic edema and brain infarctions. It was found that with treatment of the purinergic ligand 2-methylthioladenosine 5' diphosphate (2-MeSADP), which is an agonist and has a high preference for the purinergic receptor type 1 isoform (P2Y1R), significantly contributes to the reduction of an ischemic lesions caused by cytotoxic edema. Further pharmacological evidence has suggested that 2MeSADP protection is controlled by enhanced astrocyte mitochondrial metabolism through increased inositol triphosphate-dependent calcium release. There is evidence suggesting a relationship between the levels of ATP and cytotoxic edema, where low ATP levels are associated with an increased prevalence of cytotoxic edema. It is believed that mitochondria play an essential role in the metabolism of astrocyte energy within the penumbra of ischemic lesions. By enhancing the source of ATP provided by mitochondria, there could be a similar 'protective' effect for brain injuries in general.[17]
Effects on diabetes
Purinergic receptors have been implicated in the vascular complications associated with diabetes due to the effect of high-glucose concentration on ATP-mediated responses in human fibroblasts.[18]
See also
- Purinergic signaling
References
- ^ PMID 12270951.
- ^ PMID 22879061.
- S2CID 10616782.
- ^ King BF, Burnstock G (2002) Purinergic receptors. In: Pangalos M, Davies C (eds) Understanding G protein-coupled receptors and their role in the CNS. Oxford University Press, Oxford, pp 422– 438
- PMID 24865948.
- PMID 22547202.
- S2CID 25734771.
- S2CID 19142246.
- PMID 33396540.
- ^ Neuroscience. 2nd edition. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Sunderland (MA): Sinauer Associates; 2001.
- S2CID 26035589.
- PMID 19515262.
- PMID 20562826.
- S2CID 4358793.
- S2CID 32284927.
- S2CID 21486673.
- PMID 21203502.
- PMID 11079743.
External links
- IUPHAR GPCR Database – Adenosine receptors
- IUPHAR GPCR Database – P2Y receptors
- Purinergic+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)