» Articles » PMID: 37047682

The Signaling Pathway of the ADP Receptor P2Y in the Immune System: Recent Discoveries and New Challenges

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2023 Apr 13
PMID 37047682
Authors
Affiliations
Soon will be listed here.
Abstract

P2Y is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y in the cells of the immune system and the effect of P2Y activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.

Citing Articles

The role of the P2X7 receptor in inactivated SARS-CoV-2-induced lung injury.

Carvalho-Barbosa N, Cristina-Rodrigues F, Temerozo J, Souza T, Gouvea A, Canetti C Purinergic Signal. 2024; .

PMID: 39607622 DOI: 10.1007/s11302-024-10062-7.


Impact of P2Y12 inhibitors on clinical outcomes in sepsis-3 patients receiving aspirin: a propensity score matched analysis.

Jiang S, Xu J, Ke C, Huang P BMC Infect Dis. 2024; 24(1):575.

PMID: 38862910 PMC: 11167871. DOI: 10.1186/s12879-024-09421-x.


Platelets, inflammation, and purinergic receptors in chronic kidney disease.

Corken A, Ong V, Kore R, Ghanta S, Karaduta O, Pathak R Kidney Int. 2024; 106(3):392-399.

PMID: 38821448 PMC: 11343655. DOI: 10.1016/j.kint.2024.03.033.


The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

Tsoupras A, Gkika D, Siadimas I, Christodoulopoulos I, Efthymiopoulos P, Kyzas G Pharmaceuticals (Basel). 2024; 17(5).

PMID: 38794197 PMC: 11124379. DOI: 10.3390/ph17050627.


A role for platelets in metabolic reprogramming of tumor-associated macrophages.

Kang Y, Amoafo E, Entsie P, Beatty G, Liverani E Front Physiol. 2023; 14:1250982.

PMID: 37693009 PMC: 10484008. DOI: 10.3389/fphys.2023.1250982.

References
1.
Ganbaatar B, Fukuda D, Salim H, Nishimoto S, Tanaka K, Higashikuni Y . Ticagrelor, a P2Y12 antagonist, attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein-E-deficient mice. Atherosclerosis. 2018; 275:124-132. DOI: 10.1016/j.atherosclerosis.2018.05.053. View

2.
Liverani E, Rico M, Garcia A, Kilpatrick L, Kunapuli S . Prasugrel metabolites inhibit neutrophil functions. J Pharmacol Exp Ther. 2012; 344(1):231-43. PMC: 3533408. DOI: 10.1124/jpet.112.195883. View

3.
Yu X, Yu C, He W . Emerging trends and hot spots of NLRP3 inflammasome in neurological diseases: A bibliometric analysis. Front Pharmacol. 2022; 13:952211. PMC: 9490172. DOI: 10.3389/fphar.2022.952211. View

4.
Remijn J, Wu Y, Jeninga E, IJsseldijk M, Willigen G, de Groot P . Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood. Arterioscler Thromb Vasc Biol. 2002; 22(4):686-91. DOI: 10.1161/01.atv.0000012805.49079.23. View

5.
Matsuno H, Tokuda H, Ishisaki A, Zhou Y, Kitajima Y, Kozawa O . P2Y12 receptors play a significant role in the development of platelet microaggregation in patients with diabetes. J Clin Endocrinol Metab. 2004; 90(2):920-7. DOI: 10.1210/jc.2004-0137. View