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Chemical Compound Review

ADP beta S     [[(2R,3R,4R,5R)-5-(6- aminopurin-9-yl)-3,4...

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Disease relevance of ADP beta S

  • Pretreatment with pertussis toxin inhibits the action of UTP and ATP by maximally 45-55%, whereas it has no effect on the ADP beta S response [1].

High impact information on ADP beta S

  • Forskolin synergistically enhanced cAMP generation in response to ADP beta S or PGE(2), implying that, like PGE(2), ADP beta S activates adenylyl cyclase via G(s), a conclusion supported by results showing ADP beta S and MT-ADP promoted activation of adenylyl cyclase activity in MDCK-D(1) membranes [2].
  • The most potent antagonist of ATP-induced release is Coomassie Blue (IC50 = 25 microM), compared to ADP beta S (IC50 = 500 microM) [3].
  • When cP2Y(11) receptors are expressed in canine thymocyte (CF2Th) cells that normally lack functional purinergic responses, ADP beta S stimulates phosphatidylinositol (PI) hydrolysis, Ca(2+) mobilization, and cAMP accumulation [4].
  • To assess whether differences in the degree of receptor reserve might explain this discrepancy of results, P2Y1 receptor-expressing 1321N1 cells were incubated for 24 hr with adenosine-5'-O-(2-thiodiphosphate), with the goal of down-regulating the level of functional receptors [5].
  • ADP bound at both sites was competed with ADP, ATP, and ATP-alpha-S with affinities in a rank order similar to that found for platelets (ATP-alpha-S approximately ATP approximately ADP > or = ADP-beta-S approximately adenosine), suggesting the presence of a P2T receptor on CMK 11-5 cells [6].

Biological context of ADP beta S

  • The action of ATP was mimicked by ADP and the poorly hydrolyzable analogues, ADP beta S and 2-methylthio ATP, but not by beta, gamma-methylene ATP, AMP, or adenosine, indicating that the receptor mediating the actions of ATP on microglial gene expression is probably of the P2Y-purinoreceptor type [7].
  • ATP and ADP beta S competed at both binding sites with different affinities, 60 fold and 175 fold, respectively [8].
  • 2. On the pancreatic vascular bed, ADP beta S (1.5 and 15 microM) infused for 30 min induced a concentration-dependent vasodilatation; it was progressive during the first 10 min (first period) and sustained from 10 to 30 min (second period) [9].
  • Results show increased intraglomerular platelet aggregation in nephritic rats treated with ADP beta S, whereas 2chloro-ADO inhibits aggregation significantly as compared with nephritic rats receiving saline [10].
  • Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), when given alone depressed the EPSP and in addition antagonized the effect of ADP-beta-S [11].

Anatomical context of ADP beta S


Associations of ADP beta S with other chemical compounds


Gene context of ADP beta S

  • However, treatment using ATP plus PPADS or with ADP-beta-S led to marked expression of COX-2 [20].
  • These responses were attributed to P2Y2/4 and P2Y1 receptors, which we assumed could be selectively activated by UTP and ADP-beta-S respectively [18].
  • 6. The findings suggest that in the rat anococcygeus, smooth muscle cells are endowed with two distinct P2-purinoceptors which subserve contractions: a P2X-purinoceptor activated by ATP and its analogues, and another type of P2-purinoceptor activated by ADP beta S [21].
  • The combined stimulation of astrocytes with calcitonin gene-related peptide and adenosine-5'-O-(2-thiodiphosphate) resulted in the potentiated expression of c-fos messenger RNA [14].
  • The putative P2Y antagonist RB-2 had no effect against ADP beta S-induced contraction [22].

Analytical, diagnostic and therapeutic context of ADP beta S


  1. Two distinct P2 purinergic receptors, P2Y and P2U, are coupled to phospholipase C in mouse pineal gland tumor cells. Suh, B.C., Son, J.H., Joh, T.H., Kim, K.T. J. Neurochem. (1997) [Pubmed]
  2. P2Y11 receptors activate adenylyl cyclase and contribute to nucleotide-promoted cAMP formation in MDCK-D(1) cells. A mechanism for nucleotide-mediated autocrine-paracrine regulation. Torres, B., Zambon, A.C., Insel, P.A. J. Biol. Chem. (2002) [Pubmed]
  3. ATP receptor. A putative receptor-operated channel in PC-12 cells. Sela, D., Ram, E., Atlas, D. J. Biol. Chem. (1991) [Pubmed]
  4. Cloning, expression, signaling mechanisms, and membrane targeting of P2Y(11) receptors in Madin Darby canine kidney cells. Zambon, A.C., Brunton, L.L., Barrett, K.E., Hughes, R.J., Torres, B., Insel, P.A. Mol. Pharmacol. (2001) [Pubmed]
  5. Agonist action of adenosine triphosphates at the human P2Y1 receptor. Palmer, R.K., Boyer, J.L., Schachter, J.B., Nicholas, R.A., Harden, T.K. Mol. Pharmacol. (1998) [Pubmed]
  6. Functional expression of a P2T ADP receptor in Xenopus oocytes injected with megakaryocyte (CMK 11-5) RNA. Greco, N.J. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  7. Calcitonin gene-related peptide and ATP induce immediate early gene expression in cultured rat microglial cells. Priller, J., Haas, C.A., Reddington, M., Kreutzberg, G.W. Glia (1995) [Pubmed]
  8. Characterization of [35S]-ATP alpha S and [3H]-alpha, beta-MeATP binding sites in rat brain cortical synaptosomes: regulation of ligand binding by divalent cations. Schäfer, R., Reiser, G. Br. J. Pharmacol. (1997) [Pubmed]
  9. Study of the mechanisms involved in adenosine-5'-O-(2-thiodiphosphate) induced relaxation of rat thoracic aorta and pancreatic vascular bed. Saïag, B., Hillaire-Buys, D., Chapal, J., Petit, P., Pape, D., Rault, B., Allain, H., Loubatières-Mariani, M.M. Br. J. Pharmacol. (1996) [Pubmed]
  10. Modulation of anti-Thy1 nephritis in the rat by adenine nucleotides. Evidence for an anti-inflammatory role for nucleotidases. Poelstra, K., Heynen, E.R., Baller, J.F., Hardonk, M.J., Bakker, W.W. Lab. Invest. (1992) [Pubmed]
  11. P2Y(1) receptor activation inhibits NMDA receptor-channels in layer V pyramidal neurons of the rat prefrontal and parietal cortex. Luthardt, J., Borvendeg, S.J., Sperlagh, B., Poelchen, W., Wirkner, K., Illes, P. Neurochem. Int. (2003) [Pubmed]
  12. Hypotonic stimulation induced Ca2+ release from IP3-sensitive internal stores in a green monkey kidney cell line. Ishii, T., Hashimoto, T., Ohmori, H. J. Physiol. (Lond.) (1996) [Pubmed]
  13. Adenosine-5'-O-(2-thiodiphosphate) is a potent agonist at P2 purinoceptors mediating insulin secretion from perfused rat pancreas. Bertrand, G., Chapal, J., Puech, R., Loubatières-Mariani, M.M. Br. J. Pharmacol. (1991) [Pubmed]
  14. Stimulation of P2Y-purinoceptors on astrocytes results in immediate early gene expression and potentiation of neuropeptide action. Priller, J., Reddington, M., Haas, C.A., Kreutzberg, G.W. Neuroscience (1998) [Pubmed]
  15. Ap4A and ADP-beta-S binding to P2 purinoceptors present on rat brain synaptic terminals. Pintor, J., Díaz-Rey, M.A., Miras-Portugal, M.T. Br. J. Pharmacol. (1993) [Pubmed]
  16. Stimulation of insulin secretion and improvement of glucose tolerance in rat and dog by the P2y-purinoceptor agonist, adenosine-5'-O-(2-thiodiphosphate). Hillaire-Buys, D., Bertrand, G., Chapal, J., Puech, R., Ribes, G., Loubatières-Mariani, M.M. Br. J. Pharmacol. (1993) [Pubmed]
  17. Characterization of diadenosine tetraphosphate (Ap4A) binding sites in cultured chromaffin cells: evidence for a P2y site. Pintor, J., Torres, M., Castro, E., Miras-Portugal, M.T. Br. J. Pharmacol. (1991) [Pubmed]
  18. P2Y receptor-mediated Ca2+ signalling in cultured rat aortic smooth muscle cells. Pediani, J.D., McGrath, J.C., Wilson, S.M. Br. J. Pharmacol. (1999) [Pubmed]
  19. Contribution of P2-purinoceptors to neurogenic contraction of rat urinary bladder smooth muscle. Hashimoto, M., Kokubun, S. Br. J. Pharmacol. (1995) [Pubmed]
  20. Differential activation of subtype purinergic receptors modulates Ca(2+) mobilization and COX-2 in human microglia. Choi, H.B., Hong, S.H., Ryu, J.K., Kim, S.U., McLarnon, J.G. Glia (2003) [Pubmed]
  21. Evidence for two distinct P2-purinoceptors subserving contraction of the rat anococcygeus smooth muscle. Najbar, A.T., Li, C.G., Rand, M.J. Br. J. Pharmacol. (1996) [Pubmed]
  22. ADP beta S induces contraction of the human isolated urinary bladder through a purinoceptor subtype different from P2X and P2Y. Palea, S., Corsi, M., Pietra, C., Artibani, W., Calpista, A., Gaviraghi, G., Trist, D.G. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  23. Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia. Wang, X., Kim, S.U., van Breemen, C., McLarnon, J.G. Cell Calcium (2000) [Pubmed]
  24. P2 receptor-types involved in astrogliosis in vivo. Franke, H., Krügel, U., Schmidt, R., Grosche, J., Reichenbach, A., Illes, P. Br. J. Pharmacol. (2001) [Pubmed]
  25. Comparison of P2 receptor subtypes producing dilation in rat intracerebral arterioles. Horiuchi, T., Dietrich, H.H., Hongo, K., Dacey, R.G. Stroke (2003) [Pubmed]
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