Table 1.

Role of purinoreceptors and ectonucleotidases in regulating extracellular vesicles and physiological/pathological consequences.

Receptors or enzyme involved	EVs type and source	Purinergic agonist/antagonist	Effect on EVs release and cargo	Physiological and pathological impacts
P2Y12	Platelets-derived EVs	ADP agonist	↑EVs release	Pro-coagulation	[59]
		Ticagrelor antagonist	↓EVs release
	Platelet-derived EVs	PSB-0739 antagonist	↓ EVs release		[60]
P2Y1	Platelet-derived EVs	MRS2179 antagonist	↓ EVs release		[59]
P2X7-dependent NLRP3 inflammasome activation	Macrophage-derived exosome	ATP agonist	Loading IL-1β in released exosome	Inflammation	[79,80]
	Macrophage exosome	ATP agonist	↑MHC-II containing exosome release	Inflammation	[81]
	Macrophage Exosome	ATP agonist	↑CD14 release of CD9+ EV	Inflammation	[82]
RILP cleavage dependent Caspase-1 activation-P2X7	Hela cells-derived exosomes		Loading specific AAUGC motif-containing miRNA in exosome	Inflammation	[85,86]
P2X7	Monocyte microvesicle	BzATP agonist	↑PS+ microvesicle release	Inflammation	[25]
	Macrophage-derived exosome	oATP antagonist	↓Exosome release	Inflammation	[98]
	Macrophage-derived exosome	ATP agonist A740003 antagonist	↑Exosomal TACE release	Inflammation	[99]
	Neuroblastoma cell line-derived EVs	BzATP agonist	ATP exocytosis		[106]
	Melanoma cells-derived exosomes/microvesicles	BzATP agonist A740003 antagonist	Increase of miR-495-3p, miR-376c-3p, and miR-6730-3p containing EVs	Pro-metastatic activity	[107]
	Small EVs of TAMR-MCF-7 cells	KN62 antagonist	↓EVs secretion	Cancer cell migration	[108]
	HuCC-T1-derived EVs	Hypermethylation of P2RX7 gene	↓CD9+ and CD81+ EVs	Tumour progression	[110]
P2X4	HCV infected hepatocyte cells	ATP agonist	↑EVs release	HCV infection	[117]
CD73	Exosome derived from plasma of head and neck cancer patients		Release of EVs expressing surface-presenting CD73	Adenosine production	[124]
	U-87 MG glioblastoma cell line-derived exosomes		Release of EVs expressing surface-presenting CD73	T Cell aerobic glycolysis inhibition promoting GBM proliferation	[126]
CD39/CD73	HT376 bladder cancer cells		Loading CD73 and CD39 in released EVs	T Cell inhibition through adenosine production	[123]
	MCF7 breast cancer cell
	Caco-2 colorectal cancer cell
	DU145 and PC3 prostate cancer cell
	Small EVs from MIA PaCa-2 pancreatic cancer cells and H1299 non-small cells		Release of EVs expressing surface-presenting CD73	Mast cell activation	[127]
	Exosome derived from plasma of head and neck cancer patients		Loading CD73 and CD39 in released EVs	Expression correlated with cancer stage	[125]
	UMSCC47 head and neck cancer cell line		Loading CD73 and CD39 in released EVs	Angiogenesis through adenosine production	[128]
	Microvesicles from bone marrow of multiple myeloma patients		Loading CD73 and CD39 in released EVs	Immunosuppression	[129]
A2A	U251 glioblastoma cell line, Mel526 metastatic melanoma cell line, MDA-MB-231 breast cancer cell line UMSCC47 head and neck cancer cell line Preglomerular vascular smooth muscle cells	CGS21680 agonist SCH442416 antagonist A2A KO	↓EVs release ↑ EV release ↑ EV release under basal end stress condition	Apoptosis of Jurkat T cell	[130]
A1	MDA-MB-231 breast cancer cell line Preglomerular vascular smooth muscle cells	CCPA agonist A1 KO	↓EVs release Constrain EV release under basal and stress metabolic condition		[130]
A3	Thyroid lobe culture Liver cell Lung cell	MRS1191 Antagonist MRS1191 Antagonist MRS1191 Antagonist	↓FADD containing EV release ↑FADD containing EV release ↑FADD containing EV release	Regulation of apoptosis	[130,131]
A2B	Thyroid lobe culture Liver cell	MRS1754 Antagonist MRS1754 Antagonist	↑FADD containing EV release ↓FADD containing EV release	Regulation of apoptosis	[130,131]
	Preglomerular vascular smooth muscle cells	A2B KO	Constrain EV release under metabolic stress condition		[130]