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)

The effect of systemically administered phencyclidine (PCP) on the extracellular concentration of aspartate (Asp) and glutamate (Glu) in the rat anterior cingulate cortex was investigated using in vivo microdialysis. PCP significantly reduced the K(+)-evoked release of Asp and Glu, while it had no effect on the basal efflux of Asp and Glu. These results suggest that PCP might inhibit excitatory amino acid (EAA) release through an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism.
J Neural Transm Gen Sect 1993
PMID:Effect of phencyclidine on endogenous excitatory amino acid release from the rat anterior cingulate cortex--an in vivo microdialysis study. 790 19

1. Active chloride transport from the stroma to the epithelial surface (tear side) accounts for 80% of the amphibian cornea short-circuit current (SCC). 2. The effect of pentachlorophenol (PCP, a wood preservative) on the bioelectric parameters of the toad Caudiverbera caudiverbera isolated cornea was studied. 3. PCP applied to the epithelial surface in the concentration range 0.3-4.3 microM caused a dose-dependent inhibition of the PD and of the SCC in 7 corneas. This inhibition was irreversible at all concentrations after several washouts. The agent had no effect when applied to the endothelial surface. 4. In 4 experiments the inhibitory effect was partly reversed by the addition of 1 microM calcium ionophore A-23187 to the epithelial surface. 5. It is concluded that PCP is an inhibitor of corneal active chloride transport and that this structure shows greater sensitivity to this agent than other tissues.
Gen Pharmacol 1993 Jul
PMID:Pentachlorophenol (PCP) inhibits ion transport in the isolated toad cornea. 822 41

We have previously shown that a single dose of PCP produces a dose-related increase in NMDA-sensitive 3H-glutamate binding in CA1 of hippocampus 24 hours later, and some regional changes in kainate binding. Here we report that dizocilpine (MK 801) (0.1 mg/kg and 1 mg/kg), a selective agonist at the PCP receptor and a noncompetitive antagonist of NMDA, produces a similar increase in NMDA-sensitive glutamate and kainate receptor binding in hippocampus 24 hours after a dose. These observations support the conclusion that blockade of glutamate-mediated transmission at the NMDA receptor selectively increases NMDA-sensitive glutamate receptor binding in CA1 of hippocampus and kainate binding in CA3 and dentate gyrus at putatively delayed time points. Several additional areas outside of hippocampus also showed receptor changes at 24 hours after MK801.
J Neural Transm Gen Sect 1995
PMID:MK801 induces late regional increases in NMDA and kainate receptor binding in rat brain. 869 41

Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia, and PCP-treated animals can serve as a model for schizophrenia. The effects of PCP on the gene expression of NVP-1, a novel Ca(2+)-binding protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%. This result suggests that alterations in Ca(2+)-binding protein may be involved in the pathology of PCP-induced psychosis and, presumably, schizophrenia.
J Neural Transm Gen Sect 1995
PMID:Delayed changes in neural visinin-like calcium-binding protein gene expression caused by acute phencyclidine administration. 874 71

Amphetamine and related drugs of abuse facilitate dopamine transmission in the striatum. This action is believed to underlie the increase in firing of striatal motor-related neurons after amphetamine administration in behaving rats. The present study extended this electrophysiological investigation to phencyclidine (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. Like amphetamine, PCP (1.0, 2.5, or 5.0 mg/kg) increased the activity of striatal motor-related neurons concomitant with behavioral activation. These effects were blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0 mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK- 801), another noncompetitive NMDA antagonist, mimicked the effect of PCP. Collectively, these results indicate that amphetamine and NMDA antagonists exert comparable effects on striatal motor-related neurons, suggesting that the response of these cells to psychomotor stimulants is regulated by a dopaminergic-glutamatergic influence.
J Neural Transm Gen Sect 1995
PMID:Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine. 874 75

Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.
J Neural Transm Gen Sect 1995
PMID:Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. 878 72

We studied the ATP dependence of NHE-1, the ubiquitous isoform of the Na+/H+ antiporter, using the whole-cell configuration of the patch-clamp technique to apply nucleotides intracellularly while measuring cytosolic pH (pHi) by microfluorimetry. Na+/H+ exchange activity was measured as the Na(+)-driven pHi recovery from an acid load, which was imposed via the patch pipette. In Chinese hamster ovary (CHO) fibroblasts stably transfected with NHE-1, omission of ATP from the pipette solution inhibited Na+/H+ exchange. Conversely, ATP perfusion restored exchange activity in cells that had been metabolically depleted by 2-deoxy-D-glucose and oligomycin. In cells dialyzed in the presence of ATP, no "run-down" was observed even after extended periods, suggesting that the nucleotide is the only diffusible factor required for optimal NHE-1 activity. Half-maximal activation of the antiporter was obtained at approximately 5 mM Mg-ATP. Submillimolar concentrations failed to sustain Na+/H+ exchange even when an ATP regenerating system was included in the pipette solution. High ATP concentrations are also known to be required for the optimal function of other cation exchangers. In the case of the Na/Ca2+ exchanger, this requirement has been attributed to an aminophospholipid translocase, or "flippase.". The involvement of this enzyme in Na+/H+ exchange was examined using fluorescent phosphatidylserine, which is actively translocated by the flippase. ATP depletion decreased the transmembrane uptake of NBD-labeled phosphatidylserine (NBD-PS), indicating that the flippase was inhibited. Diamide, an agent reported to block the flippase, was as potent as ATP depletion in reducing NBD-PS uptake. However, diamide had no effect on Na+/H+ exchange, implying that the effect of ATP is not mediated by changes in lipid distribution across the plasma membrane. K-ATP and ATP gamma S were as efficient as Mg-ATP in sustaining NHE-1 activity, while AMP-PNP and AMP-PCP only partially substituted for ATP. In contrast, GTP gamma S was ineffective. We conclude that ATP is the only soluble factor necessary for optimal activity of the NHE-1 isoform of the antiporter. Mg2+ does not appear to be essential for the stimulatory effect of ATP. We propose that two mechanisms mediate the activation of the antiporter by ATP: one requires hydrolysis and is likely an energy-dependent event. The second process does not involve hydrolysis of the gamma-phosphate, excluding mediation by protein or lipid kinases. We suggest that this effect is due to binding of ATP to an as yet unidentified, nondiffusible effector that activates the antiporter.
J Gen Physiol 1997 Feb
PMID:ATP dependence of Na+/H+ exchange. Nucleotide specificity and assessment of the role of phospholipids. 904 42

The aims of the present study were to evaluate the extent to which primary care physicians' (PCPs) identification of psychiatric distress is related to a number of nonpsychopathological factors, such as patient sociodemographic and health-related characteristics, and to assess the impact of depression on PCP identification of psychiatric distress, controlling for patient sociodemographic and health-related characteristics. Two patient samples were chosen to explore these issues: 1) patients not fulfilling any ICD-10-defined or subthreshold psychiatric diagnosis and, 2) patients with an ICD-10 diagnosis of current depression. Patients attending 46 primary care clinics during an index period were screened by the General Health Questionnaire (GHQ)-12 and selected for a second stage interview according to GHQ score. Among the 559 interviewed patients, 123 had no mental disorder and 66 had an ICD-10 current depressive disorder. Identification of psychiatric distress by the PCP was associated with retirement among subjects without mental disorders but not among depressed patients. Patient's negative overall health self-perception and severity of physical illness were significantly related to identification of psychiatric distress in the two groups, whereas neither disability nor reason for medical consultation had a significant effect. Patients with current depression, compared with those without, were 4.3 times more likely to be identified by PCPs as having psychiatric distress when adjusting for all the above nonpsychopathological variables. Patients with depression and comorbid anxiety disorders were more likely to be recognized by the PCP as compared with those with pure depression. Finally, among depressive symptoms, diurnal variation and symptoms related to suicidal tendencies were predictive of identification of psychiatric distress, whereas increase of appetite was negatively associated with PCP recognition.
Gen Hosp Psychiatry 1997 Nov
PMID:Identification of psychiatric distress by primary care physicians. 943 85

ORF 1a of Beet yellows closterovirus (BYV) encodes the domains of the papain-like proteinase (PCP), methyltransferase (MT) and RNA helicase. BYV cDNA inserts encoding the PCP-MT region were cloned in pGEX vectors next to the glutathione S-transferase gene (GST). In a 'double tag' construct, the GST-PCP-MT cDNA was flanked by the 3'-terminal six histidine triplets. Following expression in E. coli, the fusion proteins were specifically self-cleaved into the GST-PCP and MT fragments. MT-His(6) was purified on Ni-NTA agarose and its N-terminal sequence determined by Edman degradation as GVEEEA, thus providing direct evidence for the Gly(588)/Gly(589) bond cleavage. The GST-PCP fragment purified on glutathione S-agarose was used as an immunogen to produce anti-PCP monoclonal antibodies (mAbs). On Western blots of proteins from virus-infected Tetragonia expansa, the mAbs recognized the 66 kDa protein. Immunogold labelling of BYV-infected tissue clearly indicated association of the PCP with the BYV-induced membranous vesicle aggregates, structures related to closterovirus replication.
J Gen Virol 2003 Aug
PMID:Processing and subcellular localization of the leader papain-like proteinase of Beet yellows closterovirus. 1286 60

There is growing evidence from both uncontrolled and controlled clinical studies that lamotrigine (LTG) significantly augments clozapine (CLZ) in the treatment of refractory schizophrenia (RS) [Dursun, S.M., McIntosh, D., Milliken, H., 1999. Clozapine plus lamotrigine in treatment-resistant schizophrenia. Arch. Gen. Psychiatry 56, 950; Dursun, S.M., Deakin, J.F.W., 2001. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J. Psychopharmacol. 15, 297-301; Tiihonen, J., Hallikainen, T., Ryynanen, O.P., Repo-Tiihonen, E., Kotilinen, I., Eronen, M., Toivonen, P., Wahlbeck, K., Putkonen, A., 2003. Lamotrigine in treatment-resistant schizophrenia; a randomized placebo-controlled cross over trial. Biol. Psychiatry 54, 1241-1248; Kremer, I., Vass, A., Gorelik, I., Bar, G., Blanaru, M., Javitt, D.C., Heresco-Levy, U., 2004. Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biol. Psychiatry. 56, 441-446]. However, the precise mechanism of action of this synergistic augmentation between clozapine and lamotrigine remains unclear. Therefore, the goal of this research is to explore the mechanism of action of this synergistic interaction between CLZ and LTG, utilizing a pharmacological animal model of schizophrenia by using phencyclidine (PCP). The effects of CLZ plus LTG were assessed by measuring PCP-induced hyper-locomotion and stereotyped behaviours in rats. Adult male rats (250-300 g) were pre-treated via intra-peritoneal (i.p.) injection with vehicle or drug 30 min before a PCP (5 mg/kg) or saline challenge. The behaviours were recorded and analysed for a 90-min period using the Etho Vision-computer based system. PCP produced hyper-locomotion, which was maximal at 30 min. LTG (10 mg/kg) significantly increased hyperlocomotion induced with PCP. However, a combination treatment of CLZ (5 mg/kg) plus LTG (10 mg/kg) significantly blocked the potentiation of PCP-induced hyper-locomotion observed with LTG (10 mg/kg) alone. Furthermore, the PCP-induced locomotion in the combination CLZ plus LTG-treated rats was significantly decreased when compared to vehicle. Therefore, LTG at doses that do not induce ataxia enhanced PCP-induced hyper-locomotion in rats, whereas the combination of LTG and CLZ significantly decreased PCP-induced hyper-locomotion consistent with clinical data.
 ...
PMID:Effects of clozapine plus lamotrigine on phencyclidine-induced hyperactivity. 1630 24


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