Disease relevance of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• The selective P2Y1 receptor antagonist 2'-deoxy-N6-methyl-adenosine-3',5'-diphosphate (MRS2179) and the G(i) protein inhibitor pertussis toxin blocked Ca2+ increase [1].
• P2Y1-deficient mice and mice treated with the P2Y1 antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls [2].
• Venous thrombosis was slightly but significantly inhibited in MRS2179-treated rats [2].

High impact information on [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• Neurosphere cell proliferation was attenuated after application of the P2Y(1)-receptor antagonist MRS2179 and in neurospheres from P2Y(1)-receptor knockout mice [3].
• The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y(1) antagonist MRS2179 [4].
• Antagonists of the Gq-coupled P2Y1 ADP receptor, A3P5P (500 microM) and MRS2179 (100 microM), have no effect [5].
• These data, in conjunction with results obtained by using the P2 receptor antagonists TNP-ATP, PPADS and MRS2179 indicate that the current response to alpha,beta-meATP is due to P2X3 receptor activation, while the ATP-induced rise in [Ca2+]i is evoked by P2Y1 and P2Y4 receptor activation [6].
• MRS2179, a selective P2Y1 purinergic receptor antagonist, blocked both the slow EPSP and mimicry of the EPSP by exogenously applied ATP [7].

Biological context of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• A synergistic effect regarding inhibition of ADP-induced platelet activation (10 microM) was obtained with different combinations of AR-C69931MX and MRS2179 [8].
• The phosphorylation was reduced both by removal of the extracellular Ca2+ and partially or almost completely by MRS2179 or AR-C69931MX, specific antagonists of the P2Y1 and P2Y12 receptors, respectively [9].
• MRS2179, a selective P2Y1 purinergic receptor antagonist, suppressed the ATP-evoked responses in a concentration-dependent manner with an IC50 of 0.9+/-0.1 microM [10].
• Ap(5)X and Ap(6)X induced dose-dependent vasodilation that was due to P2Y(1) receptor activation, as evidenced by use of the selective P2Y(1) receptor antagonist 2'-deoxy-N(6)-methyl-adenosine 3',5'-diphosphate diammonium (MRS2179) [11].
• Finally, intravenous injection of MRS2179 resulted in inhibition of rat platelet aggregation in response to ADP and prolonged the bleeding time, in rats or mice, as compared to controls [12].

Anatomical context of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• In contrast, no inhibition of rP2Y(13) receptor was induced by the selective P2Y(1) receptor antagonist MRS2179. rP2Y(13) receptor showed highest expression levels in spleen, followed by liver and brain (with particularly high levels in cortex and striatum as reported in man), suggesting important roles in the nervous and immune systems [13].
• Application of 2meSATP elicited MRS2179-sensitive time- and voltage-dependent inward currents in the interneurons, which depolarized the cell to firing threshold [14].

Associations of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid with other chemical compounds

• Possible effects of diphosphates on P2Y1 or adenosine receptors were excluded by the inhibitors MRS2179 and 8-SPT, respectively [15].
• Endothelium-dependent, MRS2179-independent actions of uridine 5'-triphosphate in guinea pig aorta [16].

Gene context of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• 9. TCIPA induced by alphavbeta3/MT1-MMP cells was also reduced by inhibiting the generation and actions of ADP with apyrase (250 microg ml(-1)) and 2-methylthio-AMP (2-MeSAMP) (30 microm), but not N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) (30 microm) [17].
• Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist [2].
• Blocking of the P2Y1 receptor by MRS2179 additionally increased this ADP response [9].

Analytical, diagnostic and therapeutic context of [(2R,3S,5R)-5-(6-methylaminopurin-9-yl)-3-phosphonooxy-oxolan-2-yl]methoxyphosphonic acid

• Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of alpha,betameATP-induced inward current in whole-cell recording, P2X(7) and P2Y(1) were identified as the main ionotropic and metabotropic P2 receptors active in OPs [4].
• In contrast, the height was reduced to 5.4 +/- 2.2 and 3.3 +/- 1.3 microm, respectively (p < 0.01, n = 8), when the blood used in the second 6-min perfusion contained a P2Y1 (MRS2179) or P2Y12 (AR-C69931MX) inhibitor [18].

References