Disease relevance of Methylthio-adenosine diphosphate

• 4. The inhibition of adenylyl cyclase by 2-MeSADP was completely abolished by pertussis toxin [1].
• Whole-cell patch-clamp recordings from cultured rat dorsal root ganglion neurons demonstrated that the P2Y1 receptor agonists adenosine 5'-O-2-thiodiphosphate (ADP-beta-S) and 2-methylthio adenosine 5'-diphosphate (2-MeSADP) inhibit the alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP)-induced P2X3 receptor-currents [2].

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

• 3. The selective P2Y(1) agonist, 2-MeSADP, induced a potent vasodilatation (pEC(50)=6.9+/-0.1) [8].

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

• Perfusion of cotyledons with 2-MeSADP or UTP evoked concentration-dependent reductions in perfusion pressure mediated by the NO-cGMP pathway [18].
• Reverse transcriptase-polymerase chain reaction analysis revealed that during this culture period, there was a decline in the ability to detect transcripts for P2Y(12) and P2Y(13) receptors, both of which are activated by 2-MeSADP and negatively coupled to adenylyl cyclase [12].

References