2-methylthio ATP

Ap4A, diadenosine tetraphosphate BBG, Brilliant blue green BzATP, 2 - 3 -0-(4-benzoyl-benzoyl)-ATP cAMP, cyclic AMP CCPA, chlorocyclopentyl adenosine CPA, cyclopentyl adenosine CTP, cytosine triphosphate DPCPX, 8-cyclopentyl-1,3-dipnopylxanthine IP3, inosine triphosphate lpsl, diinosine penta phosphate a,p-meATP, a,p-methylene ATP p.y-meATP, p.y-meihylene ATP 2-MeSADP, 2-methylthio ADP 2-MeSAMP, 2-methylthio AMP 2-MeSATP, 2-methylthio ATP NECA, 5 -W-ethylcarboxamido adenosine PPADS, pyridoxal-phosphate-6-azophenyl-2, 4 -disulfonic acid PLC, phospholipase C RB2, reactive blue 2 TNP-ATP, 2, 3 -0-(2,4,6-trinitrophenyl) ATP. 

P2Y, (P2Y1) receptors have been cloned from human and several other mammalian and non-mammalian species, and show an apparent functionai order of potency ATP = ADP > AMP, and seiective agonists include 2-methylthio-ATP which is more potent than ADP also ADPpp, ADPPS and 2-hexylthloATP. These receptors are found in a number of tissues inciuding intestinal smooth muscle, endothelial cells and hepatocytes. Normally they couple to the InsPs/DAG system. Recently, expression studies have provided evidence that this receptor type may also account for at least some of... 

Rat vagus nerve, a, 3-methylene ATP as agonist [54], Guinea-pig aorta, 2-methylthio ATP as agonist [55]. Rat vas deferens [54]. iApparent pKg, derived fi-om a double-reciprocal regression. PPADS interacted with two affinity states of the P2X"Puri" PfO for [ H]a,p -methylene ATP. 

Relaxant responses to 2-methylthio ATP in the carbachol-contracted rat duodenum were antagonized by PPADS (10 - 100 pM) in a concentration-related manner. The resulting Schild plot was linear and its slope (1.02) was not significantly difiTerent fi-om unity, indicating competitive antagonism. The affinity estimate for PPADS in rat duodenum (pA2 = 5.09 Table 3) was very similar to that obtained for pyridoxal-5-phosphate in guinea-pig aorta (5.39), but clearly lower compared to the apparent pKg values obtained for the P2X subtype in rabbit vas deferens (6.34) and rat mesenteric artery (6.38 Table 3). In rat mesenteric arterial bed, the tone of which was raised by methoxamine, vasodilator responses to 2-methylthio ATP were slightly inhibited by 10 pM PPADS (pA2 = 5.46), a concentration which virtually abolished P2X punnoceptor-mediated vasoconstriction. It is noteworthy that PPADS (30 pM) was found to be ineffective at vascular P2Y-punnoceptors in rabbit mesenteric artery and aorta. These results clearly demonstrate that PPADS is less effective at duodenal and vascular P2Y purinoceptors than at P2X-receptors (Table 3). 

Figure 4. Schild plots for the antagonism by PPADS in the carbachol-contracted guinea-pig taenia coli using a, P-methylene ATP (a,P-mATP) and 2-methylthio ATP (2-MeSATP) as agonists. Lines, which connect the mean log (DR - 1) values at the respective PPADS concentration, are drawn to highlight the biphasic nature of the Schild plots. The slopes of the overall regression lines (not shown) were 1.46 for a,p-mATP and 0.58 for 2-MeSATP. These values were significantly different from unity.

Relaxant responses to electrical field stimulation (0.5 - 16 Hz) in guinea-pig taenia coli were inhibited by PPADS at the same concentration-range as were the responses to exogenous ATP and 2-methylthio ATP (Figure 4) [31], In the presence of 100 pM PPADS, these neurogenic relaxations were (compared to controls) 10% (0.5 Hz), 6% (2 Hz), 5% (8 Hz) and 4% (16 Hz). This supports the purinergic nerve hypothesis, which postulates ATP or a related compound as NANC-transmitter [2]. 

P2Y ADP/3F, ATPXS 2 methylthio ATP GPCR Gj and G j coupled Suramin, PPADS... 

Methylthio-ADP (49) is a selective agonist foi the platelet P2Y3 efficacy. (47) is much more effective than ATP at P2Y4> slightly more effective than ATP at P2Y5... 

Subtypes of adenosine receptors exist - A, Aj and A3 -which have differential sensitivities to adenosine nucleoside analogues, including 2-methylthio-AMP, 2-thioadenosine, DPMA. IB-MECA, NECA, CPA. CCPA and DPCPX. These receptors, and subtypes within A2, have all been cloned. They have structures typical of the seven-transmembrane G-protein-coupled superfamily of receptors, but have amongst the shortest sequences known (A3 has only 318 amino acids), and a lack of sequence similarity with any other receptors appears to put them in a class of their own. Adenosine receptors are not sensitive to nucleotides such as ADP (adenosine diphosphate) and ATP (adenosine triphosphate), which instead act as P2 receptor agonists that are nucleotide-... 

S ATP + 5-methylthioribose (<1> enzyme may be involved in an alternative pathway of methionine synthesis in plant tissues [1] <2> may be a primary enzyme involved in the recycling of the methylthio group of 5-methylthioribose back into methionine [2,3] <3> key step in recycling of methionine from 5 -methylthioadenosine a co-product of polyamine biosynthesis, expression of methylthioribose kinase may be under control of the methionine regulon [4]) (Reversibility [1-4, 6]) [1-4, 6, 7]... 

Fig, 7. Pathways for the metabolism of methionine to 5 -methylthioadenosine (MTA) and recycling of MTA to methionine. Methionine can serve as a carbon source for the synthesis of polyamines and, in some tissues, ethylene. 5 -Methylthioadenosine is a product of both processes. Only the methylthio group of methionine is recycled, the C4 moiety for the resynthesis of methionine being derived from the ribosyl moiety of ATP. The enzymes involved are (1) SAM synthetase, (2) SAM decarboxylase, (3) various C3 transfer enzymes of polyamine biosynthesis, (4) MTA nucleosidase, (5) methylthioribose kinase, (6) three( ) uncharacterized enzymes, (7) aminotransferase, and (8) aminocyciopropane carboxylate synthase. 

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