Stimulation of platelet P2Y 1 receptors by different endogenous nucleotides leads to functional selectivity via biased signalling.
Autor: | Arkless KL; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK., Pan D; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK., Shankar-Hari M; School of Immunology and Microbial Sciences, King's College London, London, UK.; Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK., Amison RT; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK., Page CP; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK., Rahman KM; Chemical Biology Group, Institute of Pharmaceutical Science, King's College London, London, UK., Pitchford SC; Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK. |
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Jazyk: | angličtina |
Zdroj: | British journal of pharmacology [Br J Pharmacol] 2024 Feb; Vol. 181 (4), pp. 564-579. Date of Electronic Publication: 2023 Feb 13. |
DOI: | 10.1111/bph.16039 |
Abstrakt: | Background and Purpose: Platelet function during inflammation is dependent on activation by endogenous nucleotides. Non-canonical signalling via the P2Y Experimental Approach: Platelets obtained from healthy human volunteers were incubated with ADP, Ap3A, NAD + , ADP-ribose, or Up4A, with aggregation and fibrinogen binding measured (examples of function during haemostasis) or before exposure to fMLP to measure platelet chemotaxis (an inflammatory function). In silico molecular docking of these nucleotides to the binding pocket of P2Y Key Results: Platelet aggregation and binding to fibrinogen induced by ADP was not mimicked by NAD + , ADP-ribose, and Up4A. However, these endogenous nucleotides induced P2Y Conclusion and Implications: Platelet function (aggregation vs motility) can be differentially modulated by biased-agonist activation of P2Y Linked Articles: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc. (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.) |
Databáze: | MEDLINE |
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