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 electrophysiological and pharmacological properties of N-methyl-D-aspartate (NMDA)-sensitive receptors expressed in Xenopus oocytes by injection of total poly(A)+RNAs (mRNAs) from the cerebellum and cerebrum of guinea pigs were compared. The inward current induced by NMDA under voltage-clamp in cerebellar mRNA-injected oocytes was depressed in a voltage-dependent fashion by Mg2+ to show a negative slope conductance and selectively antagonized by D-2-amino-5-phosphonovalerate (D-APV) and phencyclidine (PCP). Glycine (0.01-10 microM) did not potentiate NMDA-induced currents in cerebellar mRNA-injected oocytes, while it potentiated NMDA-induced currents in cerebral mRNA-injected oocytes in a dose-dependent fashion. 6-Cyano-7-nitroquinoxaline-2,3-dione and 7-chlorokynure-nate suppressed the NMDA response but significantly less potently in cerebellar mRNA-injected oocytes than in cerebral mRNA-injected oocytes. These results suggest that the NMDA-sensitive receptor expressed in Xenopus oocytes by guinea pig cerebellar mRNA resembles the cerebral NMDA receptor in its high sensitivities to Mg2+, PCP, and D-APV, but it is distinct from the cerebral NMDA receptor in responsiveness to glycine.
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PMID:Glycine-insensitive NMDA-sensitive receptor expressed in Xenopus oocytes by guinea pig cerebellar mRNA. 197 46

Recent evidence suggest that the N-methyl-D-aspartate (N-Me-D-Asp) channel is functionally and structurally associated with the phencyclidine (PCP) receptor, which mediates the psychotomimetic effects of PCP, sigma opioids, and dioxalanes. To investigate the relationship between N-Me-D-Asp and PCP receptors on a molecular level, we injected mRNA isolated from adult rat brain into Xenopus oocytes. In injected oocytes N-Me-D-Asp application (with glycine) evoked a partially desentizing inward current that was potentiated by glycine and blocked by D-(-)-amino-5-phosphonovaleric acid (D-APV), by Zn2+ and, in a voltage-dependent manner, by Mg2+. These results show that the distinguishing features of rat brain N-Me-D-Asp channels are reproduced in this translation system. In addition, kainic acid elicited a nondesensitizing inward current at short latency, and quisqualate elicited a delayed oscillatory inward current, presumably mediated by a second-messenger system. Responses to glutamate had both short-latency and delayed components. The PCP derivative N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) blocked the N-Me-D-Asp-evoked current, and its potency was comparable to its binding affinity in rat brain membranes. Onset of block required the presence of antagonist. Antagonism was stereoselective in that the active ligand dexoxadrol was a more effective blocker than its relatively inactive stereoisomer levoxadrol. adrol. Other PCP receptor ligands, (+)SKF-10,047 and MK-801, also blocked. Potencies of compounds active at N-Me-D-Asp and PCP receptors in oocytes were comparable to those obtained previously in electrophysiological and binding assays on neural tissues. These results indicate the coexpression of neuronal PCP and N-Me-D-Asp receptors in Xenopus oocytes.
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PMID:Coexpression of N-methyl-D-aspartate and phencyclidine receptors in Xenopus oocytes injected with rat brain mRNA. 283 39

The effects of phencyclidine (PCP) on the release of acetylcholine and dopamine, stimulated by excitatory amino acid agonists was examined in slices of nucleus accumbens of the rat. In slices incubated in [3H]choline or [3H]dopamine, the amount of tritium efflux produced by 1 mM N-methyl-D-aspartate (NMDA), kainic acid (KA) or quisqualic acid (QA) was compared with that produced in the presence of varying concentrations of phencyclidine. N-Methyl-D-aspartate stimulated the calcium-dependent release of both ACh and DA, which was completely inhibited by physiological concentrations of magnesium and inhibited by 2-aminophosphonovalerate (2-APV). Kainic acid- and quisqualic acid-stimulated release of ACh and DA was partially inhibited by magnesium or by 2-APV. Phencyclidine inhibited NMDA-stimulated release of ACh and DA with IC50's around 100 nM. Phencyclidine (0.1 microM) also significantly inhibited kainic acid and quisqualic acid-induced release of ACh in magnesium-free but not magnesium-containing buffer, suggesting that the effect of PCP on kainic acid- and possibly quisqualic acid-stimulated release of ACh is on that part of the response which is mediated by NMDA receptors. The results suggest that the inhibition by PCP of the release of ACh and DA in the nucleus accumbens is selective for NMDA-type receptors.
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PMID:Inhibition by phencyclidine of excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens. 288 87

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists, D-2-amino-5-phosphonovalerate (D-APV) and phencyclidine (PCP), were studied in vitro on epileptiform activity induced in magnesium-free solution in neurons of the basolateral amygdala of the rat, using intracellular recording techniques. Twenty to 30 min after switching to magnesium-free medium, spontaneous interictal-like events were observed in 33 out of 37 amygdala slices. The spontaneous interictal-like events consisted of an initial burst followed by a number of afterdischarges. Superfusion with D-APV, a competitive NMDA receptor antagonist, reversibly reduced the duration of the events was also reduced. The IC50, estimated from the graph of the concentration-response relationship, was approximately 10 microM which is close to the IC50 for the binding of D-AVP to the NMDA receptor in other regions of the brain. The effect of phencyclidine, a noncompetitive NMDA receptor antagonist, was similar to that of D-APV. These results suggest that activation of NMDA receptors plays an intrinsic role in the induction or propagation of epileptiform activity seen in magnesium-free solution in the neurons of the amygdala.
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PMID:Epileptiform activity induced by magnesium-free solution in slices of rat amygdala: antagonism by N-methyl-D-aspartate receptor antagonists. 290 76

2-Amino-5-phosphonovalerate (APV, icv) phencyclidine (PCP, ip) and scopolamine (sc) dose-dependently disrupted short term working memory in radial maze. These drugs injected before, but not after training attenuated retention of long term memory in passive avoidance task. A relation of PCP action to its antagonism at NMDA receptors may be suggested.
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PMID:Learning impairment in rats by N-methyl-D-aspartate receptor antagonists. 290 78

The central distribution of sigma sites labelled by di-o-tolylguanidine (DTG), a compound which has specific affinity for sigma sites, and its ability to produce postural movements, are consistent with the hypothesis that sigma sites may play a functional role in the regulation of movement. The aim of the present study was to evaluate the specificity of the circling behaviour induced by unilateral intranigral injection of DTG in rats. As previously described, DTG produced dose-dependent unilateral rotations (2.5-20 nmol/rat). A similar dose-dependent circling behaviour was observed with DMTG and (+) NANM (3-40 nmol/rat), compounds which bind to both sigma and PCP sites, and with haloperidol (3-20 nmol/rat) whereas raclopride and D,L-sulpiride did not elicit any circling (10 nmol/rat). DTG-induced circling after intranigral injection (10 nmol/rat) was decreased in a dose-dependent manner by rimcazole (20-40 mg/kg, i.p.), a selective ligand for sigma sites, and by BMY 14802 (3, 10, 30 mg/kg, i.p.), ifenprodil and eliprodil (1, 3, 10 mg/kg, i.p.), non-selective sigma ligands. In contrast, naloxone (1 mg/kg, s.c.) and CGS 19755 (1, 3, 10 mg/kg, i.p.) did not change the DTG-induced circling. Eliprodil failed to inhibit circling produced by compounds devoid of any affinity for sigma sites such as APV, dizocilpine or muscimol, indicating the specificity of the inhibition observed with eliprodil on the DTG-induced circling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological evidence for the involvement of sigma sites in DTG-induced contralateral circling in rats. 762 59

The present study was performed to assess the utility of excitatory amino acid (EAA) antagonists as analgesia agents. The antinociceptive activity of various classes of EAA antagonists was assessed in mechanical and thermal flexion reflexes tests, as well as in the formalin test. Additional testing assessed the motor dysfunction associated with antinociceptive dose levels of the agents used, by examining placing, grasping and righting reflexes, as well as occurrences of balance loss during locomotion. No antinociceptive activity was observed on any of the nociceptive measures for the non-NMDA receptor antagonists CNQX or L-AP-3. High doses of the non-competitive (PCP-site) NMDA receptor antagonist MK-801 and the allosteric-glycine receptor antagonist 7-CKA produced antinociception on both the mechanical and thermal flexion reflex measures, while a high dose of the competitive NMDA receptor antagonist CPP produced antinociception only on the thermal flexion reflex measure. Hyperalgesic effects on thermal flexion reflexes were obtained with all doses of the polyamine receptor antagonist ARCA, and with the highest dose of the allosteric-glycine receptor antagonist FICA. Formalin nociceptive behaviours were significantly reduced only by high doses of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists. The doses of EAA receptor antagonists which produced antinociceptive effects on any of the 3 nociceptive tests also produced evidence of motor dysfunction. Both competitive NMDA receptor antagonists (APV and CPP) produced disruptions of placing, grasping and righting reflexes, while 2 of the allosteric-glycine receptor antagonists (7-CKA and DCQX) significantly disrupted placing and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The utility of excitatory amino acid (EAA) antagonists as analgesic agents. I. Comparison of the antinociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests. 770 8

In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer. PCP, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. The characteristics of paroxysmal depolarization shifts did not change significantly by the blockade of lateral propagation of EFP. The same asynchronized pattern of EFP conduction was observed after local application of the N-methyl-D-aspartate (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local administration of haloperidol as well as NMDA before PCP application reversibly prevented appearance of multiple pacemakers. Focal application of dopamine produced an abnormal pattern of lateral conduction of EFP in 50 % of tested slices. Pacemaker failure as an indicator of functional impairment of cortical integration is the proposed mechanism for developing of schizophrenia-like psychosis associated with epilepsy. Abbreviations. APV: DL-2-amino-5-phosphono-valeric acid EEG:electroencephalogram EFP:epileptiform field potentials NMDA:N-methyl-D-aspartate PCP:phencyclidine SLPE:Schizophrenialike psychosis associated with epilepsy
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PMID:The lateral spread of epileptiform discharges in rat neocortical slices: effect of focal phencyclidine application. 1280 69

The effects of glutamate receptor agonists and antagonists on l-[(3)H]noradrenaline (NA) release were examined in cerebral cortical and hippocampal slices of mice by superfusion methods. N- Methyl- d -aspartate (NMDA) at 100 ?M significantly stimulated l-[(3)H]NA release. The NMDA-induced l-[(3)H]NA release was inhibited by Mg(2+) in a concentration-dependent manner. APV (100 ?M), phencyclidine (PCP, 10 ?M) and MK-801 (10 ?M) caused a significant inhibition in the NMDA (100 ?M)-induced l-[(3)H]NA release, but (+)3-PPP did not. Enhancement by NMDA of a high K(+)-evoked l-[(3)H]NA release was suppressed by APV (200 ?M), PCP (1 ?M) and MK-801 (1 ?M). In contrast, quisqualate (QA, 10 and 100 ?M) and kainate (KA, 10 and 100 ?M) stimulated the release in the presence of Mg(2+). QA-induced release was inhibited by the toxin of Nephila maculata (1 ?M), a Papua New Guinean spider (NSTX), and l-glutamic acid diethyl ester (100 and 500 ?M). NMDA, QA and KA did not affect the l-[(3)H]NA uptake into brain slices, but (+)3-PPP, PCP and MK-801 inhibited the uptake with the order of inhibitory potency of PCP > (+)3-PPP ? MK-801. It is suggested that the NMDA receptor channel complex evokes NA release and enhances a depolarization-induced NA release without the regulation of the uptake. Opiate sigma (?)-receptors, however, may be involved in the uptake of NA.
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PMID:Involvement of glutamate receptor subtypes in l-[(3)H]noradrenaline release from cerebral cortical and hippocampal slices of mice. 2050 35