Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The whole-cell voltage-clamp technique was used to study the effects of extracellular ATP on smooth muscle cells isolated from the rat vas deferens. 2. ATP (1-200 microM) elicited an inward-rectifying current that was rapid in onset (less than or equal to 100 ms), reached a peak value that depended on [ATP], and desensitized in the continued presence of ATP (half-time approximately 2 s). 3. Cells recovered from desensitization when incubated in the absence of ATP (resensitization half-time approximately 2 min). 4. A comparison was made of the ability of ATP and several of its structural analogues to stimulate inward current at a negative holding potential. ATP was by far the most effective compound among the series ATP, ADP, AMP, adenosine, GTP, UTP and ITP. ADP elicited a current that was 20-25% as large as that produced by ATP, while the other compounds were ineffective at a concentration which produced a maximal ATP response. 5. AMP-CPP (alpha, beta-methylene ATP), AMP-PCP (beta, gamma-methylene ATP), and AMP-PNP (beta, gamma-imido ATP), which are relatively resistant to hydrolysis, were similarly compared to ATP. While none of these analogues elicited a current resembling the ATP-induced current, AMP-CPP and AMP-PNP each produced a small, relatively sustained inward current; AMP-PCP had little or no effect. 6. The ATP-sensitive conductance is cation selective, but does not appear to discriminate strongly between Na+, K+ and Mg2+. 7. Analysis of the fluctuations which accompany the ATP-induced current suggests that ATP controls a population of channels with a unitary current greater than 0.5 pA at -130 mV. 8. The ATP-evoked current discussed in this report may be responsible for the depolarizing effect of ATP previously described in multicellular preparations of the vas deferens.
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PMID:An ATP-sensitive conductance in single smooth muscle cells from the rat vas deferens. 245 75

Using a 'patch-clamp' method in the 'inside-out' configuration, ATP, ADP, AMP-PCP and AMP-PNP have been shown to increase the cGMP-dependent component of the rod plasma membrane conductance 2-4-fold and GTP, GDP but not GMP or nonhydrolyzable GTP analogs GMP-PNP and GTP-gamma-S to abolish the ATP action. The ATP and GTP effects were observed at [EDTA] = 1 mM when magnesium and calcium ions were absent. In about half of the experiments the cGMP-dependent conductance was shown to be increased by cAMP in the micromolar concentration range by 10-50%, the cAMP action did not depend on the presence of nucleoside triphosphates. In vivo ATP, GTP and cAMP are assumed to modulate the sensitivity of the photoreceptor plasma membrane to cGMP.
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PMID:The effect of ATP, GTP and cAMP on the cGMP-dependent conductance of the fragments from frog rod plasma membrane. 253 57

When added to intact C6 glioma cells in the micromolar range of concentrations, ADP and ATP induce an inhibition of the isoproterenol-elicited cAMP responses. ATP is rapidly hydrolyzed by the ectonucleotidases present on these cells, with an apparent Km of 50 microM and a Vmax of 1.1 nmol/min/10(6) cells. cAMP responses are also inhibited by millimolar concentrations of either ATP in the presence of an ATP-regenerating system to prevent ADP accumulation or AMP-PCP. These observations show that, in C6 glioma cells, ADP is a more potent inhibitor of cAMP production than ATP, the latter acting indirectly, via its rapid hydrolysis to ADP. The additive inhibition of isoproterenol-elicited cAMP responses induced, on one hand, by the treatment of the cells with a phorbol ester and by addition of ADP to the cells, and, on the other hand, by the progressive disappearance of the effects of ADP and ATP when cells are treated with increasing concentrations of Pertussis toxin, demonstrate that ADP and ATP exert their action in C6 glioma cells via a P2 purinoceptor probably negatively coupled to adenylate cyclase and a G regulatory protein.
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PMID:ADP and, indirectly, ATP are potent inhibitors of cAMP production in intact isoproterenol-stimulated C6 glioma cells. 255 Dec 69

(1-Aminoethyl)boronic acid (Ala-B), an analogue of alanine in which a boronic acid group replaces the carboxyl group, has been synthesized and found to inhibit the first two enzymes, alanine racemase (from Bacillus stearothermophilus, EC 5.1.1.1) and D-alanine:D-alanine ligase (ADP-forming) (from Salmonella typhimurium, EC 6.3.2.4), of the D-alanine branch of bacterial peptidoglycan biosynthesis. In both cases, time-dependent, slow binding inhibition is observed due to the generation of long-lived, slowly dissociating complexes. Ala-B inhibits alanine racemase with a Ki of 20 mM and a kappa inact of 0.15-0.35 min-1. Time-dependent loss of activity is paralleled by conversion of the 420-nm chromophore of initial bound PLP aldimine to a 324-nm absorbing species. On dilution of Ala-B, racemase activity is regained with a t1/2 of ca. 1 h. The D-Ala-D-Ala ligase also shows progressive inhibition by Ala-B provided ATP (but not AMP-PNP or AMP-PCP) is present. The presence of D-alanine along with ATP also leads to Ala-B-induced inactivation. Kinetic analysis suggests Ala-B can compete with D-alanine at either of the two D-alanine binding sites, and on inactivation with Ala-B, labeled D-alanine, and labeled ATP, the inactive enzyme has stoichiometric amounts of D-alanine, ADP, Pi, and Ala-B bound. The half-life of inactive enzyme complexes varied from approximately 2 h (without D-alanine) to 4.5 days (with D-alanine). No D-Ala-D-Ala-B dipeptide was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:(1-Aminoethyl)boronic acid: a novel inhibitor for Bacillus stearothermophilus alanine racemase and Salmonella typhimurium D-alanine:D-alanine ligase (ADP-forming). 266 72

1. The inside-out configuration of the patch-clamp method was used to study the effects of MgATP, free ATP and Mg2+ on single ATP-sensitive K+ channel currents in rat pancreatic beta-cells. 2. Magnesium ions caused a marked reduction of channel activity: 5 mM-free Mg2+ produced a 50% reduction in the activity of inward currents recorded at -60 mV in symmetrical K+ concentrations. 3. Inhibition of channel activity by MgATP does not involve phosphorylation as both free ATP (i.e. ATP in the absence of divalent cations) and non-hydrolysable ATP analogues were effective inhibitors. 4. Magnesium ions produced a striking reduction in the ability of ATP (total) to inhibit channel activity. When channel activity was plotted as a function of the total ATP concentration, the Ki for channel inhibition was 4 microM in Mg2(+)-free solution, compared to a Ki of 26 microM in the presence of 2 mM-Mg2+. The shape of the relationship between channel activity and the total ATP concentration was not changed by Mg2+. When channel activity was plotted as a function of the free ATP concentration, however, Mg2+ had little effect on Ki. This suggests that free ATP is the more potent inhibitor of channel activity and that MgATP has little inhibitory effect. 5. ATP analogues that dissociate only as far as the tribasic form were also able to inhibit channel activity. This suggests that both ATP4- and ATPH3- can block the channel. 6. Like ATP, ADP was more effective at inhibiting channel activity in the absence of Mg2+, that is as the free base. The non-hydrolysable ATP analogues AMP-PNP and AMP-PCP, however, were more effective in the presence of Mg2+. 7. It is suggested that (1) the potency of inhibition is related to the amount of negative charge carried by the ion and (2) the intracellular concentration of free ATP will be an important modulator of channel activity in the intact beta-cell.
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PMID:ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions. 269 45

Glutamine synthetase of plants is the physiological target of tabtoxinine-beta-lactam, a toxin produced by several disease-causing pathovars of Pseudomonas syringae. This toxin, a unique amino acid, is an active site-directed, irreversible inhibitor of glutamine synthetase from pea. ATP is required for inactivation. Neither ADP, AMP, nor adenosine 5'-(beta,gamma-methylene)triphosphate (AMP-PCP) supports inactivation. Adenyl-5'-yl imidophosphate (AMP-PNP) is slowly hydrolyzed by glutamine synthetase to produce adenyl-5'-yl phosphoramidate (AMP-PN) and inorganic phosphate as identified by 31P NMR spectroscopic analysis. AMP-PNP also supports a slow inactivation of glutamine synthetase by tabtoxinine-beta-lactam. These data are consistent with gamma-phosphate transfer being involved in the inactivation. Completely inactivated glutamine synthetase has 0.9 mumol of toxin bound/mumol of subunit. One mumol of ATP is bound per mumol of subunit of glutamine synthetase in the absence of either the toxin or another active site-directed inhibitor, methionine sulfoximine; whereas, a 2nd mumol of either [alpha- or gamma-32P]ATP is bound per mumol of subunit when glutamine synthetase is incubated in the presence of either toxin or methionine sulfoximine until all enzyme activity is lost. These data suggest that the gamma-phosphate hydrolyzed from ATP during inactivation remains with the enzyme-inhibitor complex, as well as the ADP. The open chain form, tabtoxinine, was neither a reversible nor an irreversible inhibitor of glutamine synthetase, suggesting that the beta-lactam ring is necessary for inhibition. The inactivation of glutamine synthetase with tabtoxinine-beta-lactam is pseudo-first-order when done in buffer containing 15% (v/v) ethylene glycol. The rate constant for this reaction is 3 X 10(-2) S-1, and the Ki for the toxin is 1 mM. Removal of the ethylene glycol from the buffer allows the reaction to proceed in a non-first-order manner with the apparent rate constant decreasing with time. As the enzyme is inactivated in these conditions, the binding affinity for the toxin appears to decrease, while the Km observed for glutamate does not change.
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PMID:Inactivation of pea seed glutamine synthetase by the toxin, tabtoxinine-beta-lactam. 287 40

1. Adult female Culex pipiens and Culiseta inornata have purinergic receptors that respond to extracellular ADP and related compounds. Stimulation of these receptors caused ingestion of artificial diets. Addition of bicarbonate to the saline solvent enhanced the phagostimulatory effect. Saline-bicarbonate was as effective a solvent as blood plasma for Cx. pipiens, and was used in the dose-effect determinations. Ranking of the potencies was: ADP greater than AMP-PNP greater than ATP = AMP greater than AMP-PCP much greater than 2'dAMP greater than 2'dADP greater than 2'dATP. At 1 mM concentration, ITP, GTP, CTP, UTP, c-AMP, 2'AMP, 3'AMP, DPG, or GSH + glucose caused fewer than 50% of the insects to gorge, as did 2'3'dd-ATP, A tetra P, and AMP-CPP at 100 microM. 2. The potency ranking for Cu. inornata was: ADP greater than AMP-PNP greater than ATP greater than AMP-PCP much greater than AMP much greater than AMP-S. The concentrations required to produce the ED50 response (inducing 50% of the test insects to gorge) were much higher than those required for Cx. pipiens; however, saline, not saline-bicarbonate, was used as the solvent. With the exception of the very low potency of AMP for Cu. inornata, the ADP potency index values for the other chemicals tested on both species are similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purinergic reception by culicine mosquitoes. 290 19

The possible involvement of adenosine diphosphate (ADP) in haemostatic platelet aggregation was investigated by determining the duration of primary haemorrhage as standardized bleeding times from punctures of small mesenteric arteries in anaesthetized rats. The bleeding times were highly significantly increased by infusing into the mesenteric arterial blood flowing towards the punctures either the nucleotide-dephosphorylating enzyme apyrase or the ADP-receptor antagonists ATP, adenosine 5'-(beta,gamma-methylene)triphosphonate (AMP-PCP) or 2-methylthioadenosine 5'-(beta,gamma-methylene)triphosphonate (2-MeS-AMP-PCP). The increases in bleeding times could not be accounted for by local vasodilator effects of the agents. It is concluded that the presence of ADP through local release and/or formation at sites of vascular injury contributes significantly to haemostasis, presumably by accelerating platelet aggregation.
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PMID:Evidence for the dependence of arterial haemostasis on ADP. 290 27

When the effects of varying concentrations of ATP on the dissociation rate of the ouabain-enzyme complex were studied, the dissociation rate constant increased with increasing ATP concentrations up to 1 mM, and then decreased with further rise in ATP; indicating that ATP binds to two distinct sites on the complex. ADP and AMP-PNP had similar biphasic effects. GTP, CTP, UTP, and AMP-PCP reduced the dissociation rate. AMP and Pi had no effects. Increase in dissociation rate caused by 0.5 mM ATP was not abolished by saturating CTP, indicating the binding of CTP to only one of the two ATP sites. The data suggest the existence of separate catalytic and regulatory sites, with different affinities and nucleotide specificities.
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PMID:Coexistence of two ATP sites on the ouabain-complexed (Na+ + K+)-ATPase. 300 82

The hypothesis that the ADP-sensitive form of phosphorylated Na+, K+-ATPase contains occluded sodium ions has been tested by a procedure which involves (i) modifying the enzyme with alpha-chymotrypsin or N-ethylmaleimide (NEM) so that the ADP-sensitive form is more stable than it is in the native enzyme, (ii) phosphorylating the modified enzyme with ATP in the presence of labelled sodium ions, and (iii) forcing the phosphorylated enzyme rapidly through a cation-exchange column and measuring the labelled sodium in the effluent. The results show that ADP-sensitive phosphoenzyme prepared from alpha-chymotrypsin- or NEM-modified Na+, K+-ATPase is able to carry labelled sodium ions through a cation-exchange resin. This behaviour was not seen with native Na+, K+-ATPase or when phosphorylation was prevented by the omission of magnesium ions or by the substitution of adenylyl(beta, gamma-methylene)diphosphonate (AMP-PCP) for ATP. The occluded sodium ions were rapidly released when the phosphoenzyme was dephosphorylated by ADP. When alpha-chymotrypsin-modified enzyme was phosphorylated by ATP with 1 mM-sodium in the medium, close to three sodium ions were occluded per phospho group. The stoicheiometry at much lower sodium concentrations could not be determined satisfactorily. A consideration of the rate constants of the reactions thought to be involved in the occlusion of sodium and in the release of sodium from the occluded state shows that, so far as they are known, these constants are compatible with the hypothesis that the occluded-sodium form of the phosphoenzyme plays a central role in sodium transport through the pump.
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PMID:The occlusion of sodium ions within the mammalian sodium-potassium pump: its role in sodium transport. 608 5


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