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)

High-affinity binding sites (apparent KD 2.87 nM) for [3H]desmethylimipramine ([3H]DMI), have been demonstrated and characterized in membrane preparations of bovine adrenal medulla. The binding of [3H]DMI improved upon pretreatment of the membrane with KCl and was saturable, sodium dependent, and potently inhibited by nisoxetine and imipramine. [3H]DMI binding was also inhibited by various phencyclidine (PCP)- and (or) sigma-receptor ligands, with the following order of potency: haloperidol > rimcazole > (-)-butaclamol > dextromethorphan > MK-801 > (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) > PCP > N-(2-thienyl)cyclohexyl-3,4-piperidine (TCP) > (+)-SKF-10047 > (-)-SKF-10047. The inhibition produced by sigma ligands was not attributed to stimulation of either sigma 1- or sigma 2-receptors, owing to inactivity of the selective sigma-receptor ligands (+)-pentazocine and 1,3-di(2-tolyl)guanidine (DTG). The inhibition of [3H]DMI binding by sigma- and PCP-receptor ligands was not attributed to PCP1- or PCP2-receptor stimulation, owing to the decreased potency (100-fold) of these ligands in [3H]DMI assays compared with the affinity for brain PCP1 sites, and the ineffectiveness of the PCP2-ligand N-(1-(2-benzo(b)thiophenyl)cyclohexyl)piperidine (BTCP). Scatchard analysis of the inhibition by the sigma-ligands haloperidol and (+)-3-PPP, as well as the PCP1 receptor ligand MK-801, demonstrated noncompetitive interaction with the site bound by [3H]DMI. These studies indicate that bovine adrenomedullary membranes possess a specific receptor for the noradrenaline uptake inhibitor [3H]DMI, which is sensitive to allosteric modulation produced by PCP and sigma-ligands.
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PMID:Characterization of [3H]desmethylimipramine binding in bovine adrenal medulla: interactions with sigma- and (or) phencyclidine-receptor ligands. 133 74

The effects of the schizophrenomimetic compound phencyclidine (PCP) on baseline activity and sensory-evoked responses of noradrenergic locus coeruleus neurons were studied with extracellular single-cell recording techniques in the chloral hydrate-anaesthetized male albino rat. PCP dose-dependently decreased firing rate, induced a more regular firing pattern of the neurons, and decreased neuronal responses to a peripheral sensory stimulus (electrical stimulation of the hindpaw). These effects of PCP were significantly decreased by pretreatment with reserpine or yohimbine, indicating that the effects of PCP were largely indirect and mediated through noradrenaline, i.e. by inhibition of its re-uptake, resulting in stimulation of alpha 2 autoreceptors. The effects of PCP were, however, mimicked by dizocilpine (MK-801), a selective non-competitive antagonist at excitatory amino acid receptors of the N-methyl-D-aspartate (NMDA) sub-type, suggesting a role also for NMDA receptors in the suppression of sensory responsiveness of locus coeruleus neurons by PCP. In view of the purported physiological role of the locus coeruleus, this effect of PCP may well contribute to the psychotomimetic properties of the drug.
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PMID:Decreased sensory responsiveness of noradrenergic neurons in the rat locus coeruleus following phencyclidine or dizocilpine (MK-801): role of NMDA antagonism. 136 26

[3H]Bremazocine (5 nM), in the presence of excess unlabelled mu and delta opioid ligands labelled two anatomically distinct populations of binding sites in the bovine adrenal medulla; a high density over the peripheral adrenaline-containing region of the medulla and a lower density over the central noradrenaline-containing region. This non-mu, non-delta opioid binding was specific (diprenorphine sensitive) but did not appear to involve classical kappa (kappa 1), sigma or PCP binding sites being insensitive to high concentrations of dynorphin (1-13), 3-PPP or MK-801. A significant proportion of the binding at both locations was however sensitive to competition by U50,488H or metorphamide. These data provide further evidence to support the existence of multiple opioid binding sites in the bovine adrenal medulla.
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PMID:Localisation and pharmacological characterisation of [3H]bremazocine binding in the bovine adrenal medulla. 165 8

1. Rat brain synaptosomes and cultured bovine adrenal chromaffin cells were used to monitor the inhibitory effects of phencyclidine (PCP) and sigma (sigma)-receptor ligands on the uptake of [3H]-noradrenaline ([3H]-NA). 2. A Na(+)-dependent high affinity uptake was observed in synaptosomes (30 degrees C) and chromaffin cells (37 degrees C) with Km of 0.22 and 0.56 microM and Vmax of 2.5 pmol min-1 mg-1 protein and 0.7 pmol min-1 per 10(6) cells, respectively. 3. PCP and haloperidol inhibited the high affinity uptake with IC50 of 0.17 and 0.42 microM, respectively in synaptosomes and 0.24 and 0.47 microM, respectively in adrenal chromaffin cells. 4. A close correlation (r = 0.96) was established between the ability of various PCP and sigma-receptor ligands to inhibit [3H]-NA uptake in both systems: PCP greater than TCP greater than haloperidol greater than 3-(+)-PPP greater than MK-801 greater than or equal to (-)-butaclamol greater than (+)-SKF-10047 greater than DTG. Spiperone and opioid receptor ligands were ineffective at 20 microM. 5. These results indicate that the central and peripheral inhibitory effects of PCP and sigma-receptor ligands on [3H]-NA uptake involves a receptor (sigma 1-like) which is distinct from that (PCP2) recognized for the inhibition of [3H]-dopamine uptake by PCP.
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PMID:Role of the sigma receptor in the inhibition of [3H]-noradrenaline uptake in brain synaptosomes and adrenal chromaffin cells. 165 47

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
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PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

The non-competitive N-methyl-D-aspartate (NMDA) antagonists (channel blockers), MK 801, phencyclidine (PCP) and ketamine induced spontaneous tail-flicks in rats. Their order of relative potency (MK 801 greater than PCP greater than ketamine) corresponds to their relative affinities for the ion channel coupled to NMDA receptors. Drugs interacting with their other potential targets (sigma receptors as well as dopamine, serotonin and noradrenaline uptake sites) failed to induce spontaneous tail-flicks. In addition, the catecholamine stimulants, methylphenidate and cocaine were inactive. CPP and CGS 19755, antagonists at the NMDA recognition site, also dose dependently elicited spontaneous tail-flicks: their maximal effect was equal to that of the channel blockers. In contrast, HA-966 and ifenprodil, putative antagonists at the glycine and polyamine recognition sites, respectively, failed to elicit spontaneous tail-flicks. These data demonstrate that both antagonists of the NMDA recognition site and non-competitive blockers of the associated channel induce spontaneous tail-flicks in rats.
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PMID:Antagonists at the NMDA recognition site and blockers of the associated ion channel induce spontaneous tail-flicks in the rat. 172 59

Neuropeptide Y (NPY) and peptide YY (PYY) are known to bind with high affinity to sigma (sigma) and phencyclidine (PCP) binding sites in rat brain. The functional significance of these results was assessed by testing both peptides in an in vitro bioassay system used for studying the N-methyl-D-aspartate (NMDA) receptor and consisting of rat hippocampal slices preloaded with [3H]noradrenaline (NA) and maintained under superfusion. The addition of NMDA in the superfusion medium induced an efflux of [3H]NA from the slices and the presence of NPY and PYY produced an enhancement of the stimulating effect. These results suggest that NPY and PYY could have a modulatory role at the NMDA receptor complex through an interaction with the sigma and/or PCP receptor.
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PMID:N-methyl-D-aspartate receptor complex modulation by neuropeptide Y and peptide YY in rat hippocampus in vitro. 182 14

An acute intraperitoneal injection of phencyclidine (PCP) caused a tetrodotoxin-reversible increase in extracellular release of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dialysates from the medial frontal cortex of the rat. Moreover, there was an increase in the tissue content of DOPAC and HVA with acceleration of dopamine (DA), but not noradrenaline, utilization in the cortical area after systemic administration of PCP. These results suggest that PCP facilitates DA metabolism in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the prefrontal region.
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PMID:Phencyclidine increases extracellular dopamine metabolites in rat medial frontal cortex as measured by in vivo dialysis. 235 32

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

Nonexocytotic noradrenaline (NA) release was examined in rat cardiac synaptosomal-mitochondrial fractions prelabeled with [3H]NA (300 nM; 1 h at 37 degrees C). Ischemic conditions (1 mM iodoacetate + 2 mM NaCN; 15 min at 37 degrees C) evoked a Ca(2+)-independent release of [3H]NA from isolated synaptosomes, which represented 33.4% of total content, whereas the release evoked by 56 mM K+ was Ca2+ dependent and represented 5.8% of total content. Tyramine, phencyclidine (PCP), and rimcazole also caused important Ca(2+)-independent releases of [3H]NA (from 12 to 45% of total content) with median effective concentrations (EC50s) of 6.8, 182, and 41.8 microM, respectively. The release responses evoked by ischemic conditions, tyramine, PCP, and rimcazole were mimicked by the delta-receptor ligand, 1,3-ditolyl guanidine (DTG), and blocked by the uptake 1 inhibitor, desipramine (100 microM). The delta 1-receptors ligands, (+)-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) and (+)N-allylnormetazocine [(+)SKF-10047], were potent blockers of the release of [3H]NA evoked by ischemic conditions but not by PCP or rimcazole. These data indicate that ischemic conditions and PCP/delta 2-receptor ligands induce carrier-mediated NA efflux from cardiac sympathetic nerve terminals, whereas delta 1-receptor ligands produce marked inhibition of the ischemic response.
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PMID:Nonexocytotic noradrenaline release from rat cardiac synaptosomal-mitochondrial fractions. 930 Mar 12


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