Ticagrelor inhibits adenosine uptake in vitro and subsequently augments cardiac blood flow in a canine model of reactive hypoxia- or adenosine-induced blood flow increases. These findings suggest that ticagrelor may have additional benefits in patients with acute coronary syndrome beyond inhibition of platelet aggregation.

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1 In the present study we have classi®ed the receptor(s) mediating increases in intracellular calcium concentration ([Ca 2+ ] i ) in human washed platelets and compared the pharmacological pro®le obtained with that observed in Jurkat cells, stably transfected with a bovine P2Y 1 -receptor. 2 The P2Y 1 -receptor antagonist, adenosine-3'-phosphate-5'-phosphate (A3P5P), competitively antagonized agonist responses in both Jurkat cells, and in platelets with similar a nities (pK B of 5.8 and 6.0, respectively). 3 The selective P2Y ADP antagonist, AR-C66096, exhibited partial agonism in the Jurkat cells with an a nity (pK A ) of 4.9. This value is consistent with its known P2Y 1 -receptor activity. In platelets, AR-C66096 at a concentration (0.1 mM) approximately 100 fold greater than its known P2Y ADP receptor a nity, had no e ect on ADP-induced increases in [Ca 2+ ] i . 4 The ability of adenine nucleotide analogues to elevate [Ca 2+ ] i in the Jurkat cells was also determined. The rank order of agonist potency (p[A] 50 ) was: 2-MeSADP (8.3)42-ClATP (7.8)4ADP (7.5)=2-MeSATP (7.4)4ATPgS (6.5)4ATP (6.2), with ATP appearing to be a partial agonist. 5 The same rank order of potency was observed when similar experiments were performed in platelets. However, the absolute potencies of all the agonists and the intrinsic activities of both ATPgS and ATP were lower in platelets. 6 The operational model of agonism was used to test whether the agonist concentration-e ect pro®les obtained in these two cell types could be explained on the basis of di erences in receptor reserve. The analysis indicated that the data obtained in platelets closely resembled that predicted for a low density or poorly coupled P2Y 1 -receptor system. 7 The hypothesis that the observed partial agonist behaviour of ATP was the result of receptor activation by contaminating ADP with concomitant receptor blockade by ATP, was tested in the platelet system. This hypothesis was supported by a theoretical analysis, which yielded an a nity value for ATP similar to that obtained previously at P2Y 1 -receptors. 8 In summary, the results of this study indicate that human washed platelets contain P2Y 1 -receptors which mediate increases in [Ca 2+ ] i and that this receptor population is pharmacologically distinct from P2Y ADP -receptors.

1The effect of the A2A adenosine receptor agonist, 2-p-(-2-carboxyethyl)phenethyl-amino-5'-Nethylcarboxamidoadenosine (CGS 21680) on the potassium evoked release of [3H]-y-aminobutyric acid ([3H]-GABA) from nerve terminals derived from the caudate-putamen and the globus pallidus of the rat was compared. In both preparations CGS 21680 (1 nM) inhibited the [3H]-GABA release evoked by 15 mM KCI but had no effect on that evoked by 30 mM KCl. 2 The ability of CGS 21680 (1 nM) to inhibit the release of [3H]-GABA from striatal nerve terminals was unaffected by the presence of the GABA receptor antagonists, bicuculline (10 gM), phaclofen (1001iM) and 2-hydroxysaclofen (100ZtM). Similarly the opioid receptor antagonist, naloxone (10 fiM), the adenosine Al receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 40 nM), and the cholinoceptor antagonists, mecamylamine (10 lM) and atropine (100 nM) had no effect on this inhibition. 5 It is concluded that the A2A adenosine receptor is present on both GABAergic and cholinergic nerve terminals of the rat striatum and that in both the caudate-putamen and the globus pallidus this receptor inhibits [3H]-GABA release. No evidence was seen for a difference in the ligand binding sites of this receptor in the two groups of nerve terminals.