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)

The effects of phencyclidine (PCP) on the behavior of rats responding to a fixed-interval 1 min schedule of water delivery were determined before, during, and after a period of daily PCP injections. The effects of acute PCP on overall response rate were biphasic: low doses increased and high doses decreased rates. In addition, PCP produced a dose-related decrease in quarter-life and high doses of PCP decreased the number of reinforcers delivered. During the daily injection regimen roughly a two-fold tolerance developed to the effects of 8.0 mg/kg PCP on response rate in animals receiving either presession or post-session injections of this dose, emphasizing the predominance of pharmacological variables in PCP tolerance. However, slight differences between these groups in tolerance development and in the rate of tolerance loss demonstrate that behavioral variables can influence tolerance to the behavioral effects of PCP.
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PMID:Tolerance to the behavioral effects of phencyclidine: the importance of behavioral and pharmacological variables. 11 26

The role played by cholinergic activity in the effects of phencyclidine (PCP) on schedule-controlled responding was studied in three squirrel monkeys trained to respond on a variable-interval (VI) 100 sec schedule of food presentation. A low dose of PCP (0.08 mg/kg IM) produced small increases in rates of responding. Higher doses (0.16--0.64 mg/kg) produced dose-dependent decreases in rates of responding. Atropine (0.05--3.2 mg/kg IM) and physostigmine (0.025--0.20 mg/kg IM) caused only decreases in response rates, the dose-response curve for atropine being particularly flat over a wide range of doses. When atropine was combined with PCP, no significant interaction was obtained. When physostigmine was combined with PCP, a complex interaction was observed. Evidence fo partial antagonism of PCP by physostigmine was obtained only at the highest PCP dose tested. Atropine-physostigmine combinations resulted in response rates suggestive of antagonism.
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PMID:Effects of phencyclidine, atropine and physostigmine, alone and in combination, on variable-interval performance in the squirrel monkey. 11 14

Choice responding in a T-shaped maze has been made contingent upon whether or not rats experienced certain drug effects. The drug discriminative cues used in the present state-dependent (StD) model were those of phencyclidine (PCP) and ditran. The specificity of these cues and their possible drug inhibition and antagonism was studied. It was found that the lower the training dose used the slower the appearance of the drug discriminative formation. Transfer testings with ketamine and cyclohexamine showed that they were interchangeable with PCP. The order of their relative potency was: cyclohexamine greater than PCP greater than ketamine. Atropine transferred to ditran. Administration of compounds not structurally related to the training drugs did not show transfer. Pretreatment with parachlorphenylalanine (p-CPA) or tetrabenazine (TBZ) plus imipramine did not indicate inhibition or antagonism in PCP trained rats. Tacrine (THA) and especially physostigmine effectively antagonized the ditran-induced cues. Yohimbine and neostigmine did not.
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PMID:Drug discrimination in rats: the effects of phencyclidine and ditran. 12 31

Like ATP the analogue beta, gamma-methylene-ATP (AMP-PCP) is shown to be an inhibitor of both ADP-induced shape change and aggregation of human platelets. The effect of AMP-PCP on aggregation is not dependent on its conversion to adenosine, though in the presence of plasma adenosine is produced and the inhibitory effect is enhanced. Since AMP-PCP cannot be enzymatically cleaved at the beta, gamma-position the inhibitory effect cannot be attributed to utilisation of the analogue by a surface-located ATPase as has been suggested for ATP. Alternative explanations for the effect are considered with respect to some current theories of ADP-induced platelet aggregation.
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PMID:Inhibition of ADP-induced aggregation of human platelets by beta, gamma-methylene-ATP. 15 89

A reactive ATP analog, N6-(6-bromoacetamidohexyl)-AMP-PCP, reacted specifically with the ATP inhibitory site of rabbit skeletal muscle phosphofructokinase without affecting the active site. Modification resulted in the incorporation of 1.01 mol of the reagent per mol of enzyme subunit. The modified enzyme was insensitive to allosteric inhibition by ATP and to activation by AMP at pH 7.2, where the native enzyme exhibits allosteric kinetic behavior. These observations demonstrate that we had succeeded in obtaining PFK fixed in the T state. Using the kinetic parameters of this modified enzyme, the kinetic properties of native enzyme can be quantitatively accounted for by the allosteric model of Monod-Wyman-Changeux. Further, the reagent was shown to have reacted with a specific cysteine residue near or at the ATP inhibitory site, and the sequence around the cysteine was determined as Cys-Lys-Asp-Phe-Arg.
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PMID:Analysis of the allosteric properties of rabbit muscle phosphofructokinase by means of affinity labeling with a reactive ATP analog. 16 Apr 16

The effects of thiourea and of several substituted thioureas -- phenylthiourea, alpha-naphtylthiourea, metiamide, and burimamide -- on dynein ATPase have been studied. The substituted thioureas are over 30 times more potent than thiourea in causing enhancement of 30S dynein ATPase activity and inhibition of 14S dynein ATPase activity. The effects of thiourea and phenylthiourea can be prevented by very low concentrations of beta-mercaptoethanol or dithiothreitol. Axonemal ATPase is also enhanced by the thioureas, but the reaction proceeds more slowly than for solubilized 30S dynein. Enhancement of 30S dynein ATPase by metiamide is prevented by low (approximately 1 microM) concentrations of ATP and, less effectively, by AMP-PNP, but not by AMP-PCP even though the latter is a stronger inhibitor of 30S dynein ATPase than is AMP-PNP. The thioureas inhibit the ATP-induced decrease in turbidity (measured as delta A350) of axonemal suspensions. Inhibition of the turbidity response is also prevented by low concentrations of beta-mercaptoethanol, but, in contrast to the irreversible enhancement of ATPase activity, inhibition of the turbidity response is largely reversible. The ability of 30S dynein to rebind onto twice-extracted axonemes is not changed by treatment with phenylthiourea or metiamide. These observations indicate that the thioureas react with at least two sets of SH or S--S groups on axonemes. Reaction with the group(s) on the 30S dynein causes an apparently irreversible enhancement of ATPase activity. Reaction with another group(s) causes a reversible inhibition of the turbidity response.
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PMID:Effect of thiourea and substituted thioureas on dynein ATPase and on the turbidity response of Tetrahymena cilia. 16 92

The enhancing effect of low concentrations (eg, 8 microM) of bis(4-fluoro-3-nitrophenyl)sulfone (FNS) on 30S dynein ATPase activity is increased when 1 mM dithiothreitol (DTT) is present. The effect of FNS + DTT is optimal at pH 7.5. Activation of the latent ATPase activity of 30S dynein by FNS + DTT is partially prevented by 1--3 microM ATP. Adenylylimidodiphosphate (AMP-PNP) is less effective than ATP, while beta, gamma-methylene-adenosine triphosphase (AMP-PCP), though a much stronger inhibitor of ATPase activity than AMP-PNP, does not protect against enhancement. These results demonstrate the presence of high-affinity ATP-binding site on 30S dynein.
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PMID:A high-affinity ATP-binding site on 30S dynein. 16 93

The effects of N-1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide(SLM) on the pellet height response and ATPase activity of glycerinated Triton X-100 extracted cilia of Tetrahymena pyriformis have been studied. Preincubation of cilia with SLM caused complete inhibition of the pellet height response and an initial increase in ATPase activity followed upon longer exposure to SLM by inhibition of ATPase. The effect of SLM on extracted 30S dynein was the reverse of that for whole cilia: ATPase activity was increased when 30S dynein was added to a mixture of ATP and SLM and inhibited when the 30S dynein was preincubated with SLM. The activity of 14S dynein was only inhibited by SLM. Electron spin resonance spectra of ciliary axonemes that had reacted with SLM for various times showed that much of the covalently bound SLM was strongly immobilized even after 1 min of reaction, when ATPase activity increased twofold. The proportion of strongly immobilized label increased with longer times of reaction. Addition of ATP to SLM-labeled axonemes caused a small decrease in the height of the spectral peak corresponding to strongly immobilized label as compared with that of weakly immobilized label, indicating an increase in rotational freedom of some covalently bound label. The results suggest that ATP causes a conformation change affecting a sulfhydryl group(s) involved in the mechanochemical system. It was also shown that beta,gamma-methylene ATP(AMP-PCP) is an inhibitor of dynein ATPase. This analogue of ATP is not hydrolyzed by whole cilia or by the extracted dyneins and does not cause a pellet height response. With Mg2+ as divalent cation, AMP-PCP inhibits 30S dynein more than it inhibits 14S dynein; with Ca2+, the inhibition of 30S dynein is reduced, and there is no inhibition of 14S dynein. Under conditions where AMP-PCP inhibited 30S dynein ATPase it was much less effective than ATP in protecting against the loss of ATPase activity by SLM. Although SLM inhibited Mg2+-activated 14S and 30S dyneins in solution, it did not inhibit ciliary ATPase activity. These results support the view that at least 2 SH groups are involved in ciliary motility and that their reactivity to SH reagents depends on whether the dyneins are in situ or have been extracted.
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PMID:Effect of spin-labeled maleimide on 14S and 30S dyneins in solution and on demembranated ciliary axonemes. 19 83

Columns containing ribosomes translating poly(U) covalently bound with cellulose (solid-phase translating system) were used to study translocation in ribosomes. It is shown that the passing of elongation factor G (EF-G) with the non-cleavable analog of GTP (GMP-PCP) through a column containing pre-translocated ribosomes results in the increase of competence for puromycin (i. e. to the transition of pre-translocated peptidyl-tRNA into the post-translocated state) just as in the case of the passing of EF-G with GTP. On the other hand, it is shown that the passing of EF-G with GMP-PCP through a column with pre-translocated ribosomes makes them capable of binding the next aminoacyl-tRNA (i. e. leads to the vacation of the ribosomal A-site). Thus, by means of the two independent tests it is shown that EF-G-promoted translocation in the ribosome can proceed without GTP hydrolysis. On the basis of the data obtained, a controlled step-wise elongation of polypeptide with the participation of EF-G without GTP cleavage has been carried out in the solid-phase column system of translation.
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PMID:[Translocation in ribosomes induced by elongation factor G without cleavage of GTP. Study using a solid phase translation system in columns]. 25 70

By means of psychiatric depth-psychological investigations in more than 100 patients with PCP the somatopsychic aspect of the disease is described, which manifests itself in two thirds of the patients as an inhibited to agitated humble-depressive psychosyndrome. On the basis of family anamneses and analytical inquiries the somatopsychic aspects of the disease is described in more the half of the patients as consistent continuation of a specific way of life, so that psychosomatic and somatopsychic aspects of the disease are mentioned as one strategy persuing the same fictitious goal. Both aspects appear as functions of a seemingly threatened psychic-physical motivity.
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PMID:[Psychosomatic and somatopsychic aspects of progressive chronic polyarthritis (author's transl)]. 28 Oct 59


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