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)

Metaphit induces audiogenic seizures in mice. The most severe clonic/tonic seizures occur 18-24 h after metaphit administration. After 48 h the incidence of the seizure episodes begin to diminish. These audiogenic seizures can be prevented by the administration of either PCP or MK-801 24 h after metaphit and 30 min prior to audio stimulation. These seizures may be due to a modulation of the PCP recognition site by metaphit which results in an enhanced probability that the NMDA/PCP ion channels are open.
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PMID:Metaphit, an isothiocyanate analog of PCP, induces audiogenic seizures in mice. 254 79

Release of both D-[3H]aspartate and endogenous amino acids was measured in primary cultures of cerebellar granule cells. Two hour-pretreatment with the glycosphingolipids, GM1 or GT1b, attenuated the stimulation of excitatory amino acid release induced by depolarizing concentrations of K+ (50 mM). Gangliosides inhibited the phencyclidine (PCP)-sensitive component of depolarization-induced release, i.e. the amplification of release that follows activation of NMDA receptors by the endogenous glutamate.
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PMID:Gangliosides attenuate NMDA receptor-mediated excitatory amino acid release in cultured cerebellar neurons. 255 58

These studies were conducted to determine whether amygdaloid kindling results in the long-term alteration of NMDA receptors which could explain the persistent reduction in seizure threshold seen in this phenomenon. NMDA-induced [3H]norepinephrine (NE) release, NMDA-sensitive L-[3H]glutamate binding, and NMDA and glycine-enhanced [3H]TCP binding were measured in brain tissue from kindled rats and nonstimulated control rats 3 to 6 weeks after the last seizure. There was no difference in the ability of NMDA to induce [3H]NE release from kindled or control slices of amygdala or hippocampus. There was also no difference in the ability of phencyclidine (PCP) or Mg2+ to inhibit [3H]NE release induced by 100 microM NMDA. Equilibrium saturation experiments of NMDA-sensitive L-[3H]glutamate binding revealed no differences in KD or Bmax values between control and kindled cortex, amygdala, and hippocampus. The Ki values for NMDA displacement of L-[3H]glutamate binding also did not differ in kindled tissue. NMDA-enhanced [3H]TCP binding was similar in cortex, amygdala, and hippocampus of kindled and control tissues. Finally, glycine-enhanced [3H]TCP binding was not different in control or kindled tissues. These studies suggest that the NMDA recognition site and the modulation of the NMDA receptor/ion channel complex by magnesium, PCP, and glycine are not altered several weeks after the last seizure. Even though NMDA-mediated electrophysiological responses are reportedly enhanced in kindled tissue at that time, the mechanism(s) underlying the enhancement remains to be determined.
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PMID:Effects of amygdaloid kindling on NMDA receptor function and regulation. 257 16

The investigation of [3H] PCP and [3H] TCP binding properties to rat cerebrum and cerebellum resulted in the demonstration of multiple binding sites for the two drugs. In the two tissue preparations PCP had a lower affinity than TCP. In membranes from the cerebrum an equal number of high affinity binding sites were present for [3H] PCP and [3H] TCP. However, low affinity binding sites were two times more numerous for [3H] PCP than for [3H] TCP. In the cerebellum, the number of high and low affinity sites labeled by the two radioligands was identical, but the number of high affinity sites was about 7 fold lower than in the cerebrum. Taken together these results may indicate that in the cerebrum [3H] PCP labels other sites than NMDA/PCP receptor(s), maybe sigma receptors and/or the dopamine uptake complex. In human cerebral cortex samples [3H] TCP also bound to two different sites. The number of high and low affinity sites were 12 and 3 times, respectively, less abundant than in the rat cerebrum. Low affinity sites were of higher affinity (5 times) than corresponding sites in the rat brain. In the human cerebellum [3H] TCP binding parameters were identical to those measured in the same region in the rat.
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PMID:Comparison of [3H] phencyclidine ([3H] PCP) and [3H] N-[1-(2-thienyl) cyclohexyl] piperidine ([3H] TCP) binding properties to rat and human brain membranes. 261 54

Quantitative autoradiographic distribution patterns of sigma/PCP and NMDA receptors show striking similarities but not in all brain areas. We have identified an endogenous ligand of brain PCP receptors which noncompetitively antagonizes NMDA-induced neurotransmitter release from brain slices. These data support the concept that the sigma/PCP receptor ligands may exert their unique behavioral effects by indirect modulation of NMDA-mediated transmission.
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PMID:Modulation of brain NMDA receptors: common mechanism of sigma/PCP receptors and their exogenous and endogenous ligands. 282 62

Neurophysiological studies have shown that glycine potentiates the NMDA response in cultured neurons by a strychnine-insensitive mechanism. Autoradiographic data have demonstrated a correspondence between strychnine-insensitive [3H]glycine binding sites and NMDA-sensitive [3H]glutamate binding sites. Here we report that in synaptic plasma membranes from rat brain, the binding of a PCP analog, [3H]TCP, was enhanced more than 5-fold by 1 microM glycine. This glycine stimulation of binding of [3H]TCP was blocked by the competitive NMDA-receptor antagonist, D-AP7. These data provide support for the hypothesis that a unique amino acid recognition site is associated with the proposed NMDA/PCP receptor complex in brain.
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PMID:Glycine modulation of the phencyclidine binding site in mammalian brain. 283 22

N-Methyl-D-aspartate (NMDA), phencyclidine (PCP), and quisqualate receptor binding were compared to benzodiazepine, gamma-aminobutyric acid (GABA), and muscarinic cholinergic receptor binding in the putamen and cerebral cortex of individuals with Huntington's disease (HD). NMDA receptor binding was reduced by 93 percent in putamen from HD brains compared to binding in normal brains. Quisqualate and PCP receptor binding were reduced by 67 percent, and the binding to other receptors was reduced by 55 percent or less. Binding to these receptors in the cerebral cortex was unchanged in HD brains. The results support the hypothesis that NMDA receptor-mediated neurotoxicity plays a role in the pathophysiology of Huntington's disease.
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PMID:NMDA receptor losses in putamen from patients with Huntington's disease. 284 62

Some unnatural opiates, which do not interact with classical opiate receptors, interact with phencyclidine (PCP) receptors. Among their many pharmacological actions, drugs which bind to the PCP receptor antagonize the actions of glutamic acid mediated via the NMDA excitatory amino acid receptor, leading to their potential use as anti-ischemic and anticonvulsant agents. Despite an enormous effort, identification of a PCP receptor antagonist, which would be useful for research and therapeutics, has not yet been reported. Chemical modification of unnatural opiates as a means to produce a PCP antagonist, or PCP agonists with properties different than PCP, has not been fully explored. Towards this end, we determined the equilibrium dissociation constants of eight enantiomeric pairs of opiates for the rat brain PCP receptor.
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PMID:Interaction of enantiomeric pairs of opiates with phencyclidine binding sites in rat brain: identification of (+) pentazocine as a ligand potentially suitable for imaging sigma binding sites using positron emission tomography. 284 88

N-Methyl-D-aspartate (NMDA)-stimulated [3H]noradrenaline release from rat hippocampal slices was blocked stereospecifically and non-competitively by MK-801 with the (+)-isomer achieving 50% blockade of 100 microM NMDA at 16 nM. The results indicate that MK-801 is the most potent NMDA antagonist yet described and that it blocks NMDA-stimulated neurotransmitter release by an action at the so-called 'phencyclidine (PCP) site'.
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PMID:Stereoselective antagonism of NMDA-stimulated noradrenaline release from rat hippocampal slices by MK-801. 284 87

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


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