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Chemical Compound Review

AC1NSJPH     tetralithium 5-amino-9-[(2S,3R,4S,5R)-3...

Synonyms:
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Disease relevance of 5-amino-9-[(2S,3R,4R,5R)-3-hydroxy-5-[(hydroxy-sulfooxy-phosphoryl)oxymethyl]-4-phosphonooxy-tetrahydrofuran-2-yl]-2,4,9-triazabicyclo[4.3.0]nona-1,3,5,7-tetraene

  • IJP-F was sensitive to the P2Y1 receptor specific antagonist A3P5PS (10muM) and to the G-protein inhibitor, pertussis toxin (PTX, 400ng/ml for 2h) as well as to the small and intermediate Ca(2+) sensitive K(+) channels blocker, apamin (0.3muM) [1].
 

High impact information on 5-amino-9-[(2S,3R,4R,5R)-3-hydroxy-5-[(hydroxy-sulfooxy-phosphoryl)oxymethyl]-4-phosphonooxy-tetrahydrofuran-2-yl]-2,4,9-triazabicyclo[4.3.0]nona-1,3,5,7-tetraene

  • SDF-1-induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS [2].
  • Following block of P2Y1 receptors with A3P5PS, co-stimulation with alpha,beta,-MeATP and ADP failed to induce aggregation despite the generation of peak [Ca2+]i responses similar to those stimulated via P2Y1 receptors [3].
  • In addition, the response was completely abolished by two specific P2Y1 receptor antagonists, namely, MRS 2179 (300 nM) and A3P5PS (10 microM) [4].
  • 2 ADPbetaS, AMPalphaS and A3P5PS behaved as partial agonists of the human P2Y11 receptor [5].
  • A3P5PS specifically inhibited 2-MeS-ADP-induced shape change and calcium increase but did not affect adenylyl cyclase down-regulation [6].
 

Biological context of 5-amino-9-[(2S,3R,4R,5R)-3-hydroxy-5-[(hydroxy-sulfooxy-phosphoryl)oxymethyl]-4-phosphonooxy-tetrahydrofuran-2-yl]-2,4,9-triazabicyclo[4.3.0]nona-1,3,5,7-tetraene

  • In order to determine if these P2Y1 receptors were involved in ADP-induced platelet activation, we determined the effects of A3P5PS, an antagonist of the P2Y1 receptor, on the binding of [33P]2-MeS-ADP, a potent analogue of ADP [6].

References

  1. NANC inhibitory neuromuscular transmission in the hamster distal colon. El-Mahmoudy, A., Khalifa, M., Draid, M., Shiina, T., Shimizu, Y., El-Sayed, M., Takewaki, T. Pharmacol. Res. (2006) [Pubmed]
  2. Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets. Kowalska, M.A., Ratajczak, M.Z., Majka, M., Jin, J., Kunapuli, S., Brass, L., Poncz, M. Blood (2000) [Pubmed]
  3. Effects of enhanced P2X1 receptor Ca2+ influx on functional responses in human platelets. Rolf, M.G., Mahaut-Smith, M.P. Thromb. Haemost. (2002) [Pubmed]
  4. Neurally released ATP mediates endothelium-dependent hyperpolarization in the circular smooth muscle cells of chicken anterior mesenteric artery. Draid, M., Shiina, T., El-Mahmoudy, A., Boudaka, A., Shimizu, Y., Takewaki, T. Br. J. Pharmacol. (2005) [Pubmed]
  5. Pharmacological characterization of the human P2Y11 receptor. Communi, D., Robaye, B., Boeynaems, J.M. Br. J. Pharmacol. (1999) [Pubmed]
  6. Role of P2Y1 purinoceptor in ADP-induced platelet activation. Savi, P., Beauverger, P., Labouret, C., Delfaud, M., Salel, V., Kaghad, M., Herbert, J.M. FEBS Lett. (1998) [Pubmed]
 
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