Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Postweaning Pb exposure has been associated with subsensitivity to the stimulus properties of the non-competitive NMDA receptor complex antagonist MK-801 (Cory-Slechta, 1995a). This study sought to determine whether Pb exposures occurring postnatally, i.e., during the primary period of development of many NMDA receptor subunits, would alter the nature of these glutamatergic system changes. Rat pups were exposed to Pb from 0-21 days of age via lactating dams consuming solutions of 0, 100 or 350 ppm Pb acetate. Beginning at 9 mos of age, rats were trained to discriminate 0.05 mg/kg MK-801 from saline using standard operant drug discrimination procedures. Following acquisition of the discrimination, various doses of MK-801, the non-competitive antagonist phencyclidine (PCP), the competitive antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP) and the agonist N-methyl-D-aspartate (NMDA) were substituted for 0.05 mg/kg MK-801 and percent MK-801 lever responding to each determined. Subsequently, a drug washout period was imposed, after which MK-801 dose-effect curves were re-established. Increasing doses of MK-801 and PCP produced dose-dependent increases in MK-801 lever responding resulting in full substitution, whereas CPP and NMDA evoked primarily saline-appropriate responding. Pb exposure was associated with enhanced MK-801 sensitivity during the pre-washout phase, but attenuated sensitivity following MK-801 washout. In both cases, however these effects were of relatively modest magnitude. No systematic Pb-related changes in response to PCP, CPP or NMDA were observed. These data raise the possibility, particularly when considered in relation to studies based on other Pb exposure protocols, that NMDA receptor changes may depend upon ongoing or extant Pb exposures, or that postnatal exposure effects on this system may be largely reversible. In addition, the differential nature of the effects seen with postnatal vs postweaning exposure (Cory-Slechta, 1995a) underscores the significance of the developmental period of exposure to Pb effects on the NMDA receptor complex.
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PMID:Postnatal lead exposure and MK-801 sensitivity. 921 3

A rapid method was developed for detecting in soil Desulfitobacterium frappieri strain PCP-1, an anaerobic gram-positive bacterium, isolated from a methanogenic consortium degrading pentachlorophenol. The method involved the establishment of a protocol for extracting total DNA from soil with the least contamination, and the use of the polymerase chain reaction (PCR) to detect strain PCP-1 with primers targeted with PCP-1 16S rRNA. To optimize the DNA extraction conditions, a glass mill homogenizer and a low-salt buffer containing polyvinylpolypyrrolidone were used on a black soil rich in organic matter. Recovered DNA was further purified with phenol/chloroform extractions, ammonium acetate precipitation and a G200 Sephadex gel-filtration column. DNA was extracted from soil supplemented with different concentrations of PCP-1 cells. Detection of PCP-1 was by PCR. The limit of detection was 800 added PCP-1 cells/g dry soil. This level of detection was achieved when the T4 gene-32 protein and 1 microgram soil DNA were added to the PCR mixture followed by a nested PCR. This method is quick, sensitive, and can process several samples at the same time.
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PMID:Rapid method for detecting Desulfitobacterium frappieri strain PCP-1 in soil by the polymerase chain reaction. 923 93

In this study the sensitivity of the acetate mineralization process performed by five strains of microorganisms in soil for the toxicants Zn2+ or PCP was calculated from the sensitivity of the contributing species. The species used were a fungus (Aspergillus niger CBS 121.49), an actinomycete (Streptomyces lividans 66), two Gram-negative Pseudomonas putida strains (MT-2 and DSM 50026) and a Gram-positive strain Rhodococcus erythropolis A177. For zinc the EC10 of the process performed by the five strains together was 77 mg/kg whereas for pentachlorophenol it was 2 mg/kg. The EC10 of the process was compared with the EC50 of the most sensitive species contributing to the process. P. putida MT2 was the most zinc sensitive strain (EC50 = 22 mg Zn/kg) and A. niger was the most sensitive strain for pentachlorophenol (EC50 = 1.4 mg/kg). This shows that a 10% inhibition of a process can be accompanied by a more than 50% inhibition of the most sensitive species.
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PMID:A comparison between toxicity tests using single species and a microbial process. 1039 Aug 42

1. Phencyclidine (PCP) is an inhibitor of the nicotinic acetylcholine receptor (AChR) with characteristics of an open-channel blocker. The location of PCP binding site on the AChR molecule is unknown. 2. PCP inhibits the AChR from electric organ with a higher potency than muscle AChR. To find the molecular basis of this difference, we expressed the two native and six hybrid receptors, and two receptors containing mutated mouse gamma subunits in Xenopus laevis oocytes. The inhibition of ACh-induced current in these receptors by PCP was studied using whole-cell voltage-clamp. All hybrid receptors generated robust ACh-induced currents, while incomplete receptors (gamma-less or delta-less) did not. 3. PCP potency was higher on hybrids containing Torpedo beta and gamma subunits regardless of the alpha and delta subunit origin. A mouse gamma subunit containing the asparagine 6' to the serine mutation in the M2 segment conferred a high sensitivity to PCP. 4. These results support the conclusion that the amino acid residues at the position 6' of the M2 segments contribute to the PCP potency difference between Torpedo and mouse receptors. 5. Another noncompetitive inhibitor of the AChR, the cembranoid eupalmerin acetate (EUAC), also inhibited the electric organ receptor with a somewhat higher potency than muscle AChR. However, the IC50 values for EUAC inhibition of hybrid receptors did not follow the pattern observed for PCP. Therefore, these two inhibitors interact differently with the AChR molecule.
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PMID:Determinants of phencyclidine potency on the nicotinic acetylcholine receptors from muscle and electric organ. 1045 35

Animal models of Pneumocystis carinii (Pc) pneumonia (PCP) play a central role in research on the Pc microorganism itself and the disease, especially the pathogenesis and the host defence. The classic rat model with corticosteroid-induced reactivation of a latent infection has been most widely used. In our search for alternative non-rodent models, six 31/2-week-old piglets were injected intramuscularly with methylprednisolone acetate, at 18 mg/kg body weight, once a week for 6 weeks. Six littermate piglets constituted the control group. The principals showed a markedly lower growth rate than the controls. Furthermore, they developed "moon face" and "pot belly", snoring sounds while eating, and pronounced respiratory distress during handling. Significant changes in haematological parameters, including lymphopenia, were observed in the principal group. The Pc antibody titres of the controls increased to high levels, whereas the principals were all low-titred or seronegative for Pc at the last blood sampling. At necropsy, the mean body weight of the principals was about half that of the controls. In addition, they had an extreme reduction of the thymus together with dark red consolidations of the frontal lung lobes and/or atelectatic looking diaphragmatic lobes. Histopathologically, there was a focal interstitial pneumonia. Alveolar walls and interstitia had mononuclear cell infiltrations and the alveolar lumina were occluded by foamy acidophilic honeycomb material with a varying number of Pc cysts. The reduced body weight, the thymus involution, and the lymphopenia, together with the reduced levels of specific Pc antibodies and the histomorphology of the PCP, were consistent parameters of the principal group and comparable to the findings of the classic rat model. Thus, the present study is the first to describe that prolonged administration of high doses of methylprednisolone acetate can induce PCP in piglets.
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PMID:Experimental corticosteroid induction of Pneumocystis carinii pneumonia in piglets. 1054 89

Strain TCE1, a strictly anaerobic bacterium that can grow by reductive dechlorination of tetrachloroethene (PCE) and trichloroethene (TCE), was isolated by selective enrichment from a PCE-dechlorinating chemostat mixed culture. Strain TCE1 is a gram-positive, motile, curved rod-shaped organism that is 2 to 4 by 0.6 to 0.8 microm and has approximately six lateral flagella. The pH and temperature optima for growth are 7.2 and 35 degrees C, respectively. On the basis of a comparative 16S rRNA sequence analysis, this bacterium was identified as a new strain of Desulfitobacterium frappieri, because it exhibited 99.7% relatedness to the D. frappieri type strain, strain PCP-1. Growth with H(2), formate, L-lactate, butyrate, crotonate, or ethanol as the electron donor depends on the availability of an external electron acceptor. Pyruvate and serine can also be used fermentatively. Electron donors (except formate and H(2)) are oxidized to acetate and CO(2). When L-lactate is the growth substrate, strain TCE1 can use the following electron acceptors: PCE and TCE (to produce cis-1,2-dichloroethene), sulfite and thiosulfate (to produce sulfide), nitrate (to produce nitrite), and fumarate (to produce succinate). Strain TCE1 is not able to reductively dechlorinate 3-chloro-4-hydroxyphenylacetate. The growth yields of the newly isolated bacterium when PCE is the electron acceptor are similar to those obtained for other dehalorespiring anaerobes (e.g., Desulfitobacterium sp. strain PCE1 and Desulfitobacterium hafniense) and the maximum specific reductive dechlorination rates are 4 to 16 times higher (up to 1.4 micromol of chloride released. min(-1). mg of protein(-1)). Dechlorination of PCE and TCE is an inducible process. In PCE-limited chemostat cultures of strain TCE1, dechlorination is strongly inhibited by sulfite but not by other alternative electron acceptors, such as fumarate or nitrate.
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PMID:Influence of different electron donors and acceptors on dehalorespiration of tetrachloroethene by Desulfitobacterium frappieri TCE1. 1058 67

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.
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PMID:Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia. 1159 34

Schizophrenia-mimicking compounds such as phencyclidine (PCP) and MK801 are antagonists at the N-methyl-D-aspartate (NMDA) receptor and produce the whole spectrum of positive, negative, and cognitive symptoms. This is one of the most important pillars of the hypoglutamatergic hypothesis of schizophrenia. Since the synthesis of glutamate and GABA in neurons is closely connected to astrocyte metabolism, the study of astrocytic function is essential in this context. Dizocilpine-maleate (MK801) (0.5 mg/kg) was injected into rats every day for 6 days. The last dose was given together with [1-(13)C]glucose and [1,2-(13)C]acetate. Extracts from frontal, retrosplenial, and cingulate cortices (CRFC) and temporal lobes were examined by (13)C nuclear magnetic resonance spectroscopy, high pressure liquid chromatography, and light microscopy. In CRFC, significant increases in the levels of glutamate, glutathione, and taurine were seen, whereas amounts and turnover of noradrenaline, dopamine, and serotonin were unchanged. Glutamate and glutamine, derived from [1,2-(13)C]acetate and thus astrocytes, were significantly decreased in CRFC as compared to controls. Labeling from [1-(13)C]glucose and thus mostly neuronal metabolism was affected in the same brain region with decreased labeling of glutamate and GABA. The present model mimics the increased glutamate/glutamine activity found in drug-naive patients with first episode schizophrenia. Moreover, the decreased labeling indicates the transition to lower glutamatergic function seen in chronic schizophrenia patients. The disturbance in astrocytic function and the glutamine-glutamate-GABA cycle are of significant importance and might add to the malfunction of the cortico-striato-thalamo-cortical loop caused by NDMA receptor blockade.
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PMID:Glial-neuronal interactions are impaired in the schizophrenia model of repeated MK801 exposure. 1639 97

Dechlorination of PCP has been observed previously under anaerobic condition in paddy soil. However, there is poor information about the dechlorination pathway of PCP and the microbial community associated with the PCP dechlorination in paddy soil. In this study, an anaerobic microbial community dechlorinating PCP was enriched by serial transfers from a paddy soil using a medium containing PCP, lactate and the steam-sterilized paddy soil. The enriched microbial community dechlorinated PCP completely to phenol under the anaerobic condition by a dechlorinating pathway as follows; PCP-->2,3,4,5-tetrachlorophenol-->3,4,5-trichlorophenol-->3,5-dichlorophenol-->3-chlorophenol-->phenol. Intermediate products such as 3-chlorophenol were not accumulated, which were immediately dechlorinated to phenol. The enriched microbial community was characterized physiologically by testing the effects of electron donors and electron acceptors on the dechlorinating activity. The dechlorinating activity was promoted with lactate, pyruvate, and hydrogen as electron donors but not with acetate. Electron acceptors, nitrate and sulphate, inhibited the dechlorinating activity competitively but not iron (III). The microbial group associated with the anaerobic dechlorination was characterized by the effect of specific inhibitors on the PCP dechlorination. Effects of specific metabolic inhibitors and antibiotics indicated the involvement of Gram-positive spore-forming bacteria with the PCP dechlorinating activity, which was represented as bacteria of phylum Firmicutes. The structure of the microbial community was characterized by fluorescence in situ hybridization, quinone profiling, and PCR-DGGE (denaturing gel gradient electrophoresis). The combined results indicated the predominance of Clostridium species of phylum Firmicutes in the microbial community. Desulfitobacterium spp. known as anaerobic Gram-positive spore-forming bacteria dechlorinating PCP were not detected by PCR using a specific primer set. These indicated a probable presence of novel anaerobic Gram-positive spore-forming bacteria dechlorinating PCP in the microbial community.
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PMID:Polyphasic characterization of a PCP-to-phenol dechlorinating microbial community enriched from paddy soil. 1747 55

The putative hydrolase gene bhp from the balhimycin biosynthetic gene cluster has been cloned and overexpressed in Escherichia coli. The corresponding enzyme Bhp was purified to homogeneity by nickel-chelating chromatography and characterized. Although Bhp has sequence similarities to hydrolases with "haloperoxidase"/perhydrolase activity, it did not show any enzymatic activity with standard "haloperoxidase"/perhydrolase substrates (e.g., monochlorodimedone and phenol red), nonspecific esterase substrates (such as p-nitrophenyl acetate, p-nitrophenyl phosphate and S-thiophenyl acetate) or the model lactonase substrate dihydrocoumarin. However, Bhp could be shown to catalyse the hydrolysis of S-beta-hydroxytyrosyl-N-acetyl cysteamine thioester (beta-OH-Tyr-SNAC) with 15 times the efficiency of S-L-tyrosyl-N-acetyl cysteamine thioester (L-Tyr-SNAC). This is in agreement with the suggestion that Bhp is involved in balhimycin biosynthesis, during which it was supposed to catalyse the hydrolysis of beta-OH-Tyr-S-PCP (PCP=peptidyl carrier protein) to free beta-hydroxytyrosine (beta-OH-Tyr) and strongly suggests that Bhp is a thioesterase with high substrate specificity for PCP-bound beta-OH-Tyr and not a "haloperoxidase"/perhydrolase or nonspecific esterase.
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PMID:The thioesterase Bhp is involved in the formation of beta-hydroxytyrosine during balhimycin biosynthesis in Amycolatopsis balhimycina. 1999


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