Platelet inhibition by P2Y₁₂ antagonists is potentiated by adenosine signalling activators

Abstract

The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions. Ethics approval statementUse of human blood samples was approved by St Thomas's Hospital Research Ethics Committee (Ref. 07/Q0702/24) and all studies were conducted in accordance with the Declaration of Helsinki. Conflict of interest disclosureThe authors state that they have no conflict of interest. Declaration of transparency and scientific rigourThis Declaration acknowledges that this paper adheres to the principles for transparent reporting and scientific rigour of preclinical research as stated in the BJP guidelines for Design and Analysis, and as recommended by funding agencies, publishers and other organisations engaged with supporting research.

Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

“…Compared with the control group, the level of ADP, ATP, TGF-β, and P-selectin in the platelets group was significantly elevated, which resulted from platelet activation via ADP contained in the culture medium of 4T1 cells. However, the level of ADP, ATP, TGF-β, and P-selectin in the platelets + Tig statistically equaled to the level of the control group, illustrating that Tig could inhibit the activation of platelets, which was consistent with previous research …”

“…However, the level of ADP, ATP, TGF-β, and P-selectin in the platelets + Tig statistically equaled to the level of the control group, illustrating that Tig could inhibit the activation of platelets, which was consistent with previous research. 60 We further investigated the effects of pDTA-Tig@CML on the interactions between platelets and tumor cells through the bioactivating release of Tig in vitro. As shown in Figure 2I, platelets adhered to tumor cells in the saline group.…”

Stimulation of platelet P2Y1 receptors by different endogenous nucleotides leads to functional selectivity via biased signalling

“…The reasons for this trend are not completely understood, but it could be that, at higher concentrations, the platelet P2Y1 receptor undergoes desensitisation and internalisation following ligand stimulation (Baurand et al ., 2005; Hardy et al ., 2005). Alternatively, high ligand concentrations might act as a self-regulatory mechanism to supress further platelet activation, since interaction between P2YR and adenosine (released or metabolised) signalling pathways (that inhibit both haemostasis and inflammatory events) has been reported (Shih et al, 2021; Layland et al, 2014). Like ADP, NAD + , ADP-ribose and Up4A induced chemotaxis via Rac1 and RhoA-dependent signalling pathways.…”

Platelets and endothelial dysfunction in gestational diabetes mellitus

“…Platelets express two types of adenosine receptors, viz., A 2A (A 2A AR) and A 2B (A 2 BAR) 42 . The binding of adenosine to its receptors causes inhibition of platelet activation and aggregation by increasing the intraplatelet levels of cAMP 43 . It is reported that the general adenosine receptors agonist 5′‐N‐ethylcarboxamidoadenosine (NECA) inhibited human platelet activation and reduced platelet aggregation and collagen secretion via inhibiting the eicosanoid lipid thromboxane A 2 (TXA 2 ) and its associated signaling 44 …”