Disease relevance of Mesatp cpd

• 4. With raised tone, and in the presence of indomethacin (10 microM) and 8-SPT (30 microM), 2-methylthio ATP (2-MeSATP) and ATP produced relaxations followed by spasms while alpha,beta-methylene ATP (alpha,beta-MeATP) induced only relaxation; all responses were concentration-dependent [1].
• Inducible nitric oxide synthase (iNOS) mRNA is up-regulated in vivo by dibutyryl-cAMP (db-cAMP), the purine-2y receptor agonist 2-methylthio-ATP and Escherichia coli endotoxin lipopolysaccharide (LPS) [2].
• The ATP analog 2-Methylthio ATP (2-MeSATP) facilitated the release of dopamine in a manner sensitive to pertussis toxin and tetrodotoxin [3].

High impact information on Mesatp cpd

• An adenine nucleotide analog, 2-methylthio-ATP, inhibited the endotoxin-stimulated release of toxic mediators (i.e., tumor necrosis factor alpha and interleukin 1), and it protected mice from endotoxin-induced death [4].
• Measurements of [Ca2+]i in single cells showed that almost all bovine aortic endothelial cells are responsive to both 2-methylthio-ATP (2MeSATP), an agonist of P2Y receptors, and UTP, an agonist of P2U receptors [5].
• UTP and 2MeSATP both stimulated the hydrolysis of phosphatidylcholine by phospholipase D, as reflected by the release of [3H]choline from prelabeled cells [5].
• Furthermore, as it was found that 2-methylthio-ATP was more potent than ATP and that beta, gamma-methylene-ATP was ineffective, the responses were mediated via the P2 gamma subtype of purinergic receptor [6].
• This reduction in the TNF-alpha to IL-10 ratio persisted to at least 24 h and is further decreased by cotreatment with 2-methylthio-ATP [7].

Biological context of Mesatp cpd

• Binding was specific, since suramin was not able to displace the binding; adenosine, ATP, UTP, alpha,beta-methylene ATP, beta,gamma-methylene ATP, ADP-betaS, 2-methylthio ATP, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) were able to displace [3H]Ap4A from its binding sites [8].
• ATP, 2-methylthio-ATP, and ADP stimulated [3H]thymidine and [3H]leucine incorporation and cell growth [9].
• 2. At basal tone nucleotides elicited dose-dependent vasoconstriction with an observed rank order of potency of alpha,beta-meATP >> 2MeSATP > ATP = ADP > UTP (based on the doses required to elicit constrictor responses of 25 mmHg) [10].
• 6. Suramin (100 microM) inhibited vasodilatation to both ATP and UTP and abolished responses to 2MeSATP [10].
• PPADS was found to block Ca2+ responses to 2-methylthio-ATP in a concentration-dependent manner with an IC50 of 0.92 +/- 0.1 microM [11].

Anatomical context of Mesatp cpd

• Other nucleotides also induced an efflux of 86Rb+ from erythrocytes with an order of agonist potency of 2'- and 3'-O(4-benzoylbenzoyl) ATP (BzATP) > ATP > 2-methylthio-ATP (2MeSATP) > adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), whereas ADP or UTP had no effect [12].
• The P2Y purinoreceptor partial agonist, 2-methylthio-ATP (2-MeS-ATP), inhibits the expression of iNOS induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) in primary macrophages [13].
• RESULTS: The nucleotide potency order was UTP > or = ATP > ITP >>> 2-methylthio-ATP > alpha,beta-methylene-ATP = beta,gamma-methylene-ATP = CTP = 0 in eosinophils [14].
• [Mol Pharmacol 53:727-733 (1998)] recently reported that, whereas ADP and 2-methylthio-ADP were agonists, ATP and 2-methylthio-ATP were weak antagonists in studies of the human P2Y1 receptor expressed in human Jurkat cells [15].
• Only four nucleotides, ATP, ATP gamma S, benzoylbenzoyl ATP (BzATP), and 2-methylthio-ATP, gave substantial stimulation of norepinephrine release from PC12 cells [16].

Associations of Mesatp cpd with other chemical compounds

• Reactive blue 2, a P2Y purinoceptor antagonist, was effective in suppressing the mitogenic effect of ATP and 2-methylthio-ATP, indicating that extracellular ATP-induced VSMC proliferation is mediated by P2Y purinoceptors [9].
• Other nucleotides tested, including beta, gamma-methylene-ATP and 2-methylthio-ATP, which are considered prototypic agonists for P2x and P2y receptors, respectively, were ineffective; in general, modifications in the ribose-triphosphate chain and substitution on the 2-position of the purines reduced the efficacy of nucleotides [17].
• Preincubation with the protein kinase C inhibitor Ro 31-8220 enhanced the subsequent inositol-1,4,5-trisphosphate response to 2MeSATP but did not affect the desensitization of this response by preincubation with the same agonist [18].
• The more relatively selective P2X agonists [beta,gamma-methylene ATP (beta,gamma-Me-ATP) and 2'- and -3'-O-(4-benzoyl-benzoyl)-ATP] inhibited arginine vasopressin (AVP)- and parathyroid hormone (PTH)-mediated Mg(2+) uptake whereas agonists more selective for P2Y purinoceptors (UTP, ADP, and 2-methylthio-ATP) were without effect [19].
• 2. At basal tone, nucleotides produced vasoconstriction with the following rank order of potency: alpha,beta-methylene ATP >> 2-methylthio ATP > or = ATP = UTP [20].

Gene context of Mesatp cpd

• Absence of the responses of alphabeta-methylene ATP and 2-methylthio-ATP excluded functionally active P2X3, P2X4, and P2Y1 receptors as far as [Ca2+]i increase is concerned [21].
• 2-Methylthio-ATP (0.1-10 microM), an agonist that can act at P2Y1 receptors, did not contract arteries or veins, whereas UTP, an agonist at rat P2Y2/P2Y4 receptors, contracted veins (EC(50) = 15 microM) and arteries (EC(50) = 24 microM) [22].
• In 1321N1 cells stably expressing the human P2Y6 receptor, the formation of IP3 was stimulated by nucleotides with the following order of potency: UDP > 5-bromo-UPT > UTP > ADP > 2-methylthio-ATP >> ATP [23].
• This effect was mediated by P2Y1 receptors because (1) 2-methylthio-ATP (2meSATP) was the most potent agonist, (2) 2'-deoxy-N6-methyladenosine-3',5'-bisphosphate diammonium (MRS2179) abolished this effect, and (3) this increase in IPSC frequency was not observed in the transgenic mice lacking P2Y1 receptor proteins [24].
• 5. While all cells tested (n = 52) responded to the P2Y-purinoceptor agonist, 2-methylthio-ATP, only a subpopulation of astrocytes (n = 67/93) was responsive to UTP [11].

Analytical, diagnostic and therapeutic context of Mesatp cpd

• 2MeSATP had relatively minor vasodilator effects and at the highest dose tested (50 nmol) elicited only vasoconstriction. alpha,beta-meATP did not elicit vasodilatation but produced further constriction of the raised tone preparation [10].
• Furthermore, the quantitative EEG after application of 2-methylthio ATP or amphetamine was characterized by an elevation of the alpha1-power [25].
• Recordings by intracellular sharp microelectrodes showed that EPSPs were concentration-dependently facilitated by the P2 receptor antagonistic ATP analogue 2-methylthio ATP (2-MeSATP), while ATP itself depressed the synaptic potentials [26].
• The basal extracellular dopamine concentration was enhanced after accumbal perfusion with the ATP analog 2-methylthio ATP (2-MeSATP; 100 microM); by contrast, adenosine (100 microM) caused a reduction of extracellular dopamine [27].
• Among some tested compounds including neuropeptide Y, both ATP and 2-methylthio ATP produced a transient contraction in the dilator muscle and the sustained treatment with each markedly attenuated the nonadrenergic responses to electrical stimulation and to ATP [28].

References