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

• Adenosine 5'-O-2-thiodiphosphate (ADP-beta-S; a P2Y receptor agonist) induced an increase in [Ca2+]i in Ca(2+)-free medium and caused phosphoinositide breakdown in COS-7 cells [12].
• Adenosine-5'-O-(2-thiodiphosphate) is a potent agonist at P2 purinoceptors mediating insulin secretion from perfused rat pancreas [13].
• 3. On 5-hydroxy tryptamine (5-HT) precontracted rings mounted in isometric conditions in organ baths, we observed that ADP beta S induced a concentration-dependent relaxation of rings with a functional endothelium; this effect was stable for 25 min [9].
• The action of adenosine-5'-O-(2-thiodiphosphate), a non-hydrolysable purine analogue and potent P2Y1-purinoceptor agonist, was studied on immediate early gene expression in rat astrocyte cultures [14].
• Ap4A and ADP-beta-S binding to P2 purinoceptors present on rat brain synaptic terminals [15].

Associations of ADP beta S with other chemical compounds

• 5. In conclusion, the P2y-agonist, ADP beta S, is a potent insulin secretagogue in vivo, improves glucose tolerance and is effective after oral administration [16].
• 3. The ATP analogues displaced [3H]-Ap4A with the potency order of the P2y receptors, adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) greater than 5'-adenylyl imidodiphosphate (AMP-PNP) greater than alpha, beta-methylene ATP (alpha, beta-MeATP), in both binding sites [17].
• Indomethacin (10 microM) delayed ADP beta S-induced vasodilatation (1.5 and 15 microM) by about 6 min [9].
• 1. ATP, UTP, ADP and ADP-beta-S elicited Ca2+ -signals in cultured aortic smooth muscle cells although ADP, UDP and ADP-beta-S gave approximately 40% of the maximal response seen with ATP and UTP [18].
• The application of 100 microM adenosine 5'-o-2-thiodiphosphate (ADP beta S) in the presence of atropine and alpha, beta-Me ATP decreased the contractile response induced by electrical stimulations to 17.15 +/- 3.71% (n = 15) of the control [19].

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

• A rapid and transient increase in c-fos, junB, c-jun and Tis11 messenger RNA was observed in cultured astrocytes after treatment with adenosine-5'-O-(2-thiodiphosphate) [14].
• In addition, perfusion of either ATP plus PPADS or ADP-beta-S alone caused a significantly enhanced duration (about 200%) of the [Ca2+]i response relative to that induced by ATP [23].
• Recordings with intracellular sharp, microelectrodes showed a concentration-dependent inhibition of the EPSP by adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) [11].
• A significant increase of both GFAP-immunoreactivity (IR) and GFA-protein content (by using Western blotting) was found after microinfusion of alpha,beta-meATP or ADP-beta-S [24].
• RESULTS: Extraluminal application of ATP-gamma-S and ADP-beta-S initiated a biphasic response (initial constriction followed by the secondary dilation) similar to ATP-induced responses [25].

References