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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

methylthio-ADP     [[(2R,3S,4R,5R)-5-(6-amino- 2...

Synonyms: CHEMBL435402, CHEBI:317939, AC1L3TRY, AR-1H6595, AC1Q6S18, ...
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Disease relevance of Methylthio-adenosine diphosphate


High impact information on Methylthio-adenosine diphosphate

  • The mutant receptors were expressed in COS-7 cells and measured for stimulation of phospholipase C induced by the potent agonist 2-methylthioadenosine-5'-diphosphate (2-MeSADP) [3].
  • UTP and 2methylthioADP (2-MeSADP), P2Y receptor agonists, also enhanced this LPS-induced TNF-alpha release [4].
  • The mutation of Y306 (7.35, site of a cationic residue in P2Y12) or Y203 in the second extracellular loop selectively decreased the affinity of the agonist 2-MeSADP, and the Y306F mutation also reduced antagonist (MRS2179) affinity by 5-fold [5].
  • Contractile responses to 2-MeSADP decreased with age, and were absent at 8 and 24 months; P2Y1 receptor expression followed this pattern [6].
  • In the ileum and colon relaxant responses to 2-MeSADP were not detected until days 8 and 12, respectively [7].

Biological context of Methylthio-adenosine diphosphate


Anatomical context of Methylthio-adenosine diphosphate

  • These results indicate that both 2-MeSADP and 2-MeSATP are agonists at the rat hepatocyte P2Y(1) receptor [9].
  • 2-MeSADP induced relaxation of the mesenteric artery, responses being greatest at 6 weeks and decreased thereafter, which was mimicked by the P2Y1 receptor immunostaining [6].
  • The stable ADP analogue 2-MeSADP decreased ATP release from red blood cells by inhibition of cAMP [10].
  • 2-MeSADP stimulated contractions in vessel segments from internal mammary artery (IM), IM branches and small veins (Emax=15+/-6% of 60 mmol/L K+ contraction, pEC50=5.6+/-0.6, Emax=21+/-1%, pEC50=6.8+/-0.1, and Emax=48+/-9%, pEC50=6.6+/-0.4) [11].

Associations of Methylthio-adenosine diphosphate with other chemical compounds

  • We conclude that 2-MeSADP regulates rat hepatocyte glycogen phosphorylase by acting on P2Y(1) receptors coupled to raised [Ca(2+)](c), and by inhibiting cyclic AMP levels by an unknown G(i)-coupled receptor subtype, distinct from P2Y(1), P2Y(12), or P2Y(13) receptors [12].
  • Based on these pharmacological characteristics and the dose-response relationships for ATP, 2 MeSATP, 2 MeSADP, ADP, and adenosine, we concluded that Müller cells express the P1A2 and P2Y1 subtypes of purinoceptors [13].
  • Here we report that 2-methylthioadenosine 5'-diphosphate (2-MeSADP), an agonist at P2Y(1), P2Y(12), and P2Y(13) receptors, potently (threshold 30 nM) stimulates glycogen phosphorylase in freshly isolated rat hepatocytes [12].

Gene context of Methylthio-adenosine diphosphate

  • P2Y1 receptor agonist concentrations that elicited aggregation (pEC50 for ADP, 2-MeSADP; 5.88, 6.69) were 10-fold greater than those that elicited SC (7.33, 7.67) [14].
  • Two types of P2Y nucleotide receptor subtypes involved in ATP-induced Ca2+ transients could be separated by application of different P2Y receptor agonists and cross desensitization experiments: P2Y1 (rank order of potency: 2-MeSADP > 2-MeSATP > ADP > ATP) and P2Y2 (sensitive to UTP and ATP) [15].
  • Concurrent replacement of three regions (N-terminus, EL1, and EL3) completely precluded activation by 2-MeSADP [16].
  • In addition, in these cells, both 2-MeSADP and UTP inhibited glucagon-stimulated cyclic AMP accumulation [12].
  • Pre-incubation of the A6-NHE3 cells with the synthetic peptide, Ht31, which prevents the binding between AKAPs and the regulatory PKA subunits RII, also prevented the 2-MeSADP-induced inhibition of NHE3 [17].

Analytical, diagnostic and therapeutic context of Methylthio-adenosine diphosphate


  1. Activity of adenosine diphosphates and triphosphates on a P2Y(T) -type receptor in brain capillary endothelial cells. Simon, J., Vigne, P., Eklund, K.M., Michel, A.D., Carruthers, A.M., Humphrey, P.P., Frelin, C., Barnard, E.A. Br. J. Pharmacol. (2001) [Pubmed]
  2. Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons. Gerevich, Z., Müller, C., Illes, P. Eur. J. Pharmacol. (2005) [Pubmed]
  3. The role of amino acids in extracellular loops of the human P2Y1 receptor in surface expression and activation processes. Hoffmann, C., Moro, S., Nicholas, R.A., Harden, T.K., Jacobson, K.A. J. Biol. Chem. (1999) [Pubmed]
  4. Bi-functional effects of ATP/P2 receptor activation on tumor necrosis factor-alpha release in lipopolysaccharide-stimulated astrocytes. Kucher, B.M., Neary, J.T. J. Neurochem. (2005) [Pubmed]
  5. Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling. Costanzi, S., Mamedova, L., Gao, Z.G., Jacobson, K.A. J. Med. Chem. (2004) [Pubmed]
  6. Changes in purinergic signalling in developing and ageing rat tail artery: importance for temperature control. Wallace, A., Knight, G.E., Cowen, T., Burnstock, G. Neuropharmacology (2006) [Pubmed]
  7. Postnatal development of P2 receptors in the murine gastrointestinal tract. Giaroni, C., Knight, G.E., Zanetti, E., Chiaravalli, A.M., Lecchini, S., Frigo, G., Burnstock, G. Neuropharmacology (2006) [Pubmed]
  8. Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor. Wihlborg, A.K., Malmsjö, M., Eyjolfsson, A., Gustafsson, R., Jacobson, K., Erlinge, D. Br. J. Pharmacol. (2003) [Pubmed]
  9. Evidence that 2-methylthioATP and 2-methylthioADP are both agonists at the rat hepatocyte P2Y(1) receptor. Dixon, C.J. Br. J. Pharmacol. (2000) [Pubmed]
  10. ADP acting on P2Y13 receptors is a negative feedback pathway for ATP release from human red blood cells. Wang, L., Olivecrona, G., Götberg, M., Olsson, M.L., Winzell, M.S., Erlinge, D. Circ. Res. (2005) [Pubmed]
  11. ADP receptor P2Y12 is expressed in vascular smooth muscle cells and stimulates contraction in human blood vessels. Wihlborg, A.K., Wang, L., Braun, O.O., Eyjolfsson, A., Gustafsson, R., Gudbjartsson, T., Erlinge, D. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  12. Regulation of rat hepatocyte function by P2Y receptors: focus on control of glycogen phosphorylase and cyclic AMP by 2-methylthioadenosine 5'-diphosphate. Dixon, C.J., Hall, J.F., Webb, T.E., Boarder, M.R. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  13. Müller cell Ca2+ waves evoked by purinergic receptor agonists in slices of rat retina. Li, Y., Holtzclaw, L.A., Russell, J.T. J. Neurophysiol. (2001) [Pubmed]
  14. Agonist concentration-dependent differential responsivity of a human platelet purinergic receptor: pharmacological and kinetic studies of aggregation, deaggregation and shape change responses mediated by the purinergic P2Y1 receptor in vitro. Maayani, S., Schwarz, T.E., Patel, N.D., Craddock-Royal, B.D., Tagliente, T.M. Platelets (2003) [Pubmed]
  15. Neuroligand-mediated calcium signaling in cultured human schwannoma cells. Mayer, C., Kamleiter, M., Sanchez-Brandelik, R., Rosenbaum, C., Kluwe, L., Hanemann, C.O., Grafe, P. J. Peripher. Nerv. Syst. (1999) [Pubmed]
  16. Shift in purine/pyrimidine base recognition upon exchanging extracellular domains in P2Y 1/6 chimeric receptors. Hoffmann, C., Soltysiak, K., West, P.L., Jacobson, K.A. Biochem. Pharmacol. (2004) [Pubmed]
  17. Extracellular adenine nucleotides regulate Na+/H+ exchanger NHE3 activity in A6-NHE3 transfectants by a cAMP/PKA-dependent mechanism. Bagorda, A., Guerra, L., Di Sole, F., Helmle-Kolb, C., Favia, M., Jacobson, K.A., Casavola, V., Reshkin, S.J. J. Membr. Biol. (2002) [Pubmed]
  18. P2Y1 and P2Y2 receptor distribution varies along the human placental vascular tree: role of nucleotides in vascular tone regulation. Buvinic, S., Poblete, M.I., Donoso, M.V., Delpiano, A.M., Briones, R., Miranda, R., Huidobro-Toro, J.P. J. Physiol. (Lond.) (2006) [Pubmed]
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