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

As a result of frequent phencyclidine (PCP) abuse, pyrolysis studies were conducted to further investigate its fate during smoking. Marijuana placebo cigarettes were impregnated with 3H-PCP X HCI and burned under conditions simulating smoking. Mainstream smoke was passed through glass wool filters as well as acidic and basic traps. Approximately 90% of the starting material could be accounted for in the first glass wool trap and cigarette holder. HPLC and GC/MS analysis of methanol extracts of these glass wool traps revealed the presence of 1-phenyl-1-cyclohexene (47% of the starting material) greater than PCP (40%) greater than piperidine (15%) greater than N-acetylpiperidine (9%). It was not possible to fully account for the remainder of the piperidine moiety. It has been reported that at high temperatures PCP is converted to numerous polynuclear aromatic compounds which include styrene, alpha-methylstyrene, naphthalene, 2-methylnaphthalene, 1-methylnaphthalene, biphenyl, cyclohexylbenzene, acenaphthene, phenanthrene, and anthracene. These compounds were not formed from PCP under smoking conditions.
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PMID:Identification and quantification of phencyclidine pyrolysis products formed during smoking. 372 75

Cultured rat hepatocytes were challenged with benzo[a]pyrene (BaP; 0.3-30 mum), naphthalene (NAPH; 0.1-100 mum), 2-methylnaphthalene (2-MNAPH; 0.1-100 mum), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001-1 nM), 2,3,7,8-tetrachlorodibenzofuran (TCDF; 0.005-5 nM) or pentachlorophenol (PCP; 0.1-100 mum) for 4-24 hr to define class-specific differences in hepatotoxic potential. Mitochondrial fragility and GSH status were monitored as indices of hepatocyte injury. A 4-hr challenge with BaP and PCP increased mitochondrial fragility in a concentration-dependent manner, while TCDD and TCDF elicited erratic increases, and NAPH and 2-MNAPH were without effect. Pretreatment of hepatocytes with 250 muM diamide enhanced the mitochondrial toxicity of BaP. The aryl hydrocarbon receptor agonists upregulated hepatocyte GSH levels by 24 hr, a response which in the case of BaP was preceded by varying degrees of GSH depletion between 6 to 16 hr. NAPH and 2-MNAPH transiently decreased hepatocyte GSH levels at 12 hr, but were without effect at later time points, while PCP did not modulate hepatocyte GSH levels. Modulation of hepatocyte GSH by BaP and TCDD was antagonized by 10 muM alpha-naphthoflavone. These data implicate oxidative mechanisms and aryl hydrocarbon receptor signalling in aromatic hydrocarbon hepatotoxicity.
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PMID:Cytotoxic response profiles of cultured rat hepatocytes to selected aromatic hydrocarbons. 2065 98

The cytotoxic responses of cultured rat renal cortico-tubular epithelial cells (TECs) and glomerular mesangial cells (GMCs) to selected polycyclic and polyhalogenated aromatic hydrocarbons (AHs) were evaluated to further define class specific differences in toxicity potential among these chemicals. Primary cultures of renal cells were exposed to benzo[a]pyrene (BaP, 0.3-30mum); naphthalene (NAPH, 1-1000mum); 2-methylnaphthalene (2-MNAPH, 1-1000mum), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.01-1nm); 2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.05-5nm; and pentachlorophenol (PCP, 0.1-10mum for 4 or 24hr. Measurements of mitochondrial membrane fragility in TECs revealed that the polycyclic aromatic hydrocarbons (PAHs) (BaP, NAPH and 2-MNAPH) preferentially injured these cells relative to halogenated aromatic hydrocarbons (HAHs). Extended exposures to all AHs tested were associated with moderate mitochondrial injury in TECs. Challenge of TECs with AHs for 4hr did not modulate GSH levels, although modest increases in this tripeptide occurred on extended exposures. Similar response profiles were observed in GMCs, where PAHs elicited mitochondrial damage by 4hr, while extended challenge was associated with injury in response to all AHs. Only aryl hydrocarbon receptor (AhR) ligands (BaP, TCDD and TCDF) depleted intracellular glutathione (GSH) in GMCs, while extended exposures to BaP and TCDD, as well as NAPH and 2-MNAPH, were associated with rebound increases in cellular GSH content. These data indicate that AHs can compromise renal cell function by interference with mitochondrial function and GSH homeostasis and implicate both epithelial and mesenchymal populations in the nephrotoxic response to this heterogeneous class of chemicals.
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PMID:Cytotoxic Response Profiles of Cultured Renal Epithelial and Mesenchymal Cells toSelected Aromatic Hydrocarbons. 2065 4

The present studies were conducted to assess cell-specific cytotoxic responses of the kidney to selected aromatic hydrocarbons (AHs) using in vitro culture systems of glomerular mesangial cells and cortical tubular epithelial cells. Primary cultures of glomerular mesangial cells or cortical tubular epithelial cells were treated for 24 hr with naphthalene (NAPH, 0.1-1000 mum), 2-methylnaphthalene (2-MNAPH, 0.1-1000 mum), benzo[a]pyrene (B[a]P, 0.3-300 mum), pentachlorophenol (PCP, 0.1-1000 mum), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.001-1 nm) or 2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.005-5 nm). [(3)H]Thymidine incorporation into DNA, cellular potassium content, and lactate dehydrogenase (LDH) leakage were used as indices of cytotoxicity. Glomerular mesangial cells exposed to NAPH or 2-MNAPH (0.1-1000 mum) exhibited [(3)H]thymidine incorporation profiles similar to those of the vehicle controls, whereas B[a]P at all concentrations and PCP at 1000 mum decreased [(3)H]thymidine incorporation in comparison with the controls. TCDD and TCDF increased [(3)H]thymidine incorporation relative to controls at 0.1 nm and 0.5 nm, respectively. Glomerular mesangial cells treated with NAPH or PCP exhibited decreased cellular potassium content and increased LDH leakage only at the 1000 mum concentration. In tubular epithelial cells, treatment with NAPH (10 or 1000 mum), 2-MNAPH (10 or 1000 mum), B[a]P (300 mum), and PCP (10 or 1000 mum) induced concentration-dependent decreases in [(3)H]thymidine incorporation relative to controls. In contrast, exposure of tubular epithelial cells to TCDD or TCDF did not modulate [(3)H]thymidine incorporation at any of the concentrations tested. A modest decrease in cellular potassium content and an increase in LDH leakage was observed at the 1000 mum concentration of PCP in tubular epithelial cells. On the basis of these data, we conclude that renal glomerular mesangial cells and tubular epithelial cells exhibit differential cytotoxic response profiles to AHs.
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PMID:Assessment of cell-specific cytotoxic responses of the kidney to selected aromatic hydrocarbons. 2069 83