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

---

Query: EC:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrophysiological studies were carried out to investigate the mechanism of action of phencyclidine [PCP; 1-(phenylcyclohexyl)piperidine] on a segmental monosynaptic reflex using isolated spinal cord preparations from neonatal rats. PCP and its related compounds produced a concentration-dependent depression of the monosynaptic reflex with a relative potency as follows: PCP = 1-[1-(2-thienyl)cyclohexyl]piperidine greater than 1-(1-m-aminophenylcyclohexyl)piperidine much greater than 1-(1-m-nitrophenylcyclo-hexyl)piperidine approximately MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] much greater than (+)-N-allylnormetazocine. The N-methyl-D-aspartate receptor antagonists 2-amino-5-phosphonovalerate and 2-amino-7-phosphonoheptanoate had no effect on the monosynaptic reflex. The depression of the monosynaptic reflex by PCP was antagonized by serotonin (5-HT) receptor antagonists (methiothepin, spiperone and ketanserin) but unaffected by noradrenergic (phentolamine and timolol), dopaminergic (chlorpromazine and pimozide) and cholinergic antagonists (atropine and mecamylamine). Whereas 5-HT and a putative 5-HT releaser, p-chloroamphetamine, also depressed the monosynaptic reflex, the blockade of monoamine uptake by imipramine did not. Furthermore, pretreatment of rats with desipramine and 5,7-dihydroxytryptamine largely diminished the depression of the monosynaptic reflex by PCP and p-chloroamphetamine while enhancing the depressant action of 5-HT. These results suggest that PCP acts at sites located on presynaptic terminals of spinal serotonergic neurons, enhancing 5-HT release and thereby depressing the monosynaptic reflex.
...
PMID:Presynaptic activation of the spinal serotonergic system in the rat by phencyclidine in vitro. 274 96

The purpose of this experiment was to investigate the interaction of GABA (gamma aminobutyric acid) with PCP (phencyclidine) and sigma receptor agonists in the cerebellum. Drugs were applied directly to a single cerebellar Purkinje neuron of urethane-anesthetized rats, through a multibarrel pipette. The PCP receptor agonist, (+)PCMP [1-(-1-phenylcyclohexyl)-3-methyl piperidine], significantly enhanced GABA-induced inhibition. On the other hand, its stereoisomer, (-)PCMP, had no such modulatory effect. Dexoxadrol, a sigma receptor agonist, similar to (+)PCMP, potentiated GABA-induced depression. Its stereoisomer, levoxadrol, although inhibiting the spontaneous firings of Purkinje neurons, did not alter the effect of GABA. In conclusion, the findings indicate that the electrophysiological mechanisms of PCP-induced facilitation of GABA-induced reactions are similar to those triggered by sigma agonists in the cerebellum.
...
PMID:Facilitation of gamma-aminobutyric acid-induced depression by (+)PCMP and dexoxadrol in the cerebellar Purkinje neurons of the rat. 274 47

The acute administration of phencyclidine (PCP) causes hypothermia in the rat. Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine) is a derivative of PCP that has been shown to irreversibly acylate PCP receptors in vitro and in vivo and can antagonize the behavioral and electrophysiological effects of PCP in the rat. The purpose of the present study was to determine whether pretreatment with metaphit can block the hypothermic effects of PCP in the rat. Metaphit or PCP (1.0 mumol/rat) were injected into the lateral ventricles of rats, and 24 hr later the subjects were challenged with PCP (20.0 mg/kg s.c.). Pretreatment with metaphit blocked PCP-induced hypothermia; however, pretreatment with PCP did not affect the subsequent hypothermic response to PCP. These results indicate that the antagonism of PCP-induced hypothermia by metaphit was a specific effect and not due to PCP receptor desensitization.
...
PMID:Metaphit antagonizes phencyclidine-induced hypothermia in the rat. 277 Apr 9

[3H]BTCP ([3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine), a phencyclidine (PCP) derivative which binds with a high affinity to the dopamine (DA) uptake complex in vitro, has been tested for in vivo binding to mouse brain. Using [3H]BTCP as a tracer (5 microCi, i.v.) we found the striatum as the region which accumulated the largest amount of radioactivity (58 dpm/mg tissue). In other brain regions the radioactive level (about 20 dpm/mg tissue) was close to the non-specific binding determined by an injection of unlabeled BTCP (40 mg/kg, s.c.) 2 h prior to the [3H]BTCP injection. In the striatum [3H]BTCP binding was inhibited in a dose-dependent manner by unlabeled BTCP (ID50 = 6.34 mg/kg) and nomifensine (ID50 = 11.06 mg/kg). It was unaffected by the DA receptor antagonist haloperidol and by PCP or its analog TCP at doses of 10 mg/kg. These results suggest that [3H]BTCP binds to the dopamine uptake complex in the mouse brain in vivo. Thus, although PCP has no effect on [3H]BTCP binding in these experimental conditions, this in vivo binding model will be useful for the determination of the precise interaction of PCP and its derivatives with the striatal dopamine uptake complex in vivo independently of their interaction with the N-methyl-D-aspartate receptor-channel complex.
...
PMID:In vivo labelling of the mouse dopamine uptake complex with the phencyclidine derivative [3H]BTCP. 277 Nov 69

Dioxadrol exists in four isomeric forms. alpha-(+)-Dioxadrol (dexoxadrol) showed phencyclidine (PCP)-like activity in rhesus monkeys trained to discriminate s.c. administration of ketamine, but neither alpha-(-)-dioxadrol (levoxadrol) nor beta-(+/-)-dioxadrol showed such activity. In addition, response-contingent i.v. dexoxadrol maintained higher rates of responding than either levoxadrol or beta-dioxadrol in monkeys experienced with ketamine self-administration. The order of potency in displacing bound 1-[1-(2-thienyl)cyclohexyl]piperidine from binding sites in rat brain homogenates was dexoxadrol much greater than levoxadrol = beta-(+/-)-dioxadrol. Viewed in the context of previous studies with stereochemical probes of the PCP receptor, these results extend and confirm the supposition that dexoxadrol and levoxadrol are the stereochemical probes of choice in the study of effects mediated through PCP receptors. The absolute configuration of dexoxadrol was determined to be 4S, 6S by X-ray crystallography, thus defining the optimum chirality necessary for receptor binding and PCP-like activity in the dioxadrol series. Based on these and other considerations, receptor-active conformations of dexoxadrol and PCP are proposed.
...
PMID:Enantiomeric and diastereomeric dioxadrols: behavioral, biochemical and chemical determination of the configuration necessary for phencyclidine-like properties. 282 92

Binding and photoaffinity labeling experiments were employed in order to differentiate 1-(1-phenylcyclohexyl)piperidine (PCP) receptor sites in rat brain. Two classes of PCP receptors were characterized and localized: one class binds [3H]-N-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) with high affinity (Kd = 10-15 nM) and the other binds the ligand with a relatively low affinity (Kd = 80-100 nM). The two classes of sites have different patterns of distribution. Forebrain regions are characterized by high-affinity sites (hippocampus greater than frontal cortex greater than thalamus greater than olfactory bulb greater than hypothalamus), but some parts (e.g., hippocampus, hypothalamus) contain low-affinity sites as well. In the cerebellum only low-affinity sites were detected. Binding sites for [3H]PCP and for its photolabile analogue [3H]azido-PCP showed a regional distribution similar to that of the [3H]TCP sites. The neuroleptic drug haloperidol did not block binding to either the high- or the low-affinity [3H]TCP sites, whereas Ca2+ inhibited binding to both. Photoaffinity labeling of the PCP receptors with [3H]AZ-PCP indicated that five specifically labeled polypeptides of these receptors (Mr 90,000, 62,000, 49,000, 40,000, and 33,000) are unevenly distributed in the rat brain. Two of the stereoselectively labeled polypeptides (Mr 90,000 and 33,000) appear to be associated with the high- and low-affinity [3H]TCP-binding sites; the density of the Mr 90,000 polypeptide in various brain regions correlates well with the localization of the high-affinity sites, whereas the density of the Mr 33,000 polypeptide correlates best with the distribution of the low-affinity sites.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Binding studies and photoaffinity labeling identify two classes of phencyclidine receptors in rat brain. 282 87

Opiate receptor subtypes in the adenohypophysis were analyzed by binding studies with tritiated etorphine, phencyclidine (PCP), and N-allylnormetazocine [(+)SKF 10,047] in anterior pituitary cell (AC) cultures and membranes, and in cell populations separated by centrifugal elutriation. In cultured AC, specific binding of [3H]etorphine revealed two sets of saturable sites with Kd values of 5 nM and about 10 microM. The high affinity [3H]etorphine sites were present in low concentration and represent specific opiate receptors that mediate the direct inhibitory actions of etorphine and morphine on LH release in vitro. The more abundant low affinity sites, observed in the presence of higher concentrations of unlabeled opiates, exhibited the properties of sigma/PCP receptors. In intact AC and pituitary membranes, specific [3H]PCP binding was saturable with respect to labeled and unlabeled ligand concentrations, and Scatchard analysis revealed a single class of relatively high affinity [3H]PCP-binding sites (Kd = 98 nM in pituitary membranes). Relative potencies derived from inhibition of [3H]PCP binding in AC by PCP-related drugs were: (-) cyclazocine greater than dexoxadrol greater than N-[1-(2-Thienyl)cyclohexil]piperidine greater than PCP greater than (+)SKF 10,047 greater than levaxodral greater than (+)cyclazocine less than (-)SKF 10,047 greater than (+)ethylketocyclazocine greater than haloperidol greater than (-)ethylketocyclazocine. In elutriated pituitary cells, specific [3H]PCP binding was correlated with the LH content of the individual cell fractions. The binding of (+)-[3H]SKF 10,047 was also specific and saturable in AC and anterior pituitary membranes, which contained two classes of binding sites with Kd values of 87 nM and 3.3 microM. In fractionated pituitary cells, specific binding of (+)-[3H]SKF 10,047 was similar in enriched lactotrophs and gonadotrophs. The high affinity class of (+)-[3H]SKF 10,047-binding sites probably corresponds to sigma-receptors, and the low affinity class to PCP receptors. In contrast to the inhibitory actions of opiates on LH release in vitro, PCP and (+)SKF 10,047 stimulated LH release in cultured AC and enhanced the secretory responses to GnRH as well as KCl. The stimulation of LH release by PCP was dependent on extracellular calcium and is probably related to increased transmembrane calcium influx. The stimulatory sites may correspond to selective sigma/PCP receptors, and could represent a distinct nonopiate receptor subtype with the potential for modulation of gonadotropin secretion.
...
PMID:Receptors and secretory actions of sigma/phencyclidine agonists in anterior pituitary cells. 282 79

MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) is a novel anticonvulsant agent reported to antagonize certain N-methyl-D-aspartate (NMDA)-mediated effects non-competitively. The question arises of the mechanism underlying the anti-NMDA and anticonvulsant effects of MK-801. In the present study MK-801 is shown to be an extremely potent inhibitor of the binding of N-[3H] (1-[2-thienyl]cyclohexyl)piperidine ([3H]TCP) to brain phencyclidine (PCP)/sigma-receptors. Its IC50 value of 3.8 +/- 0.8 nM in this assay ranks it as the most potent known ligand of brain PCP/sigma-receptors. Addition of MK-801 altered the apparent Kd but not the apparent Bmax values for [3H]TCP binding, indicating a competitive interaction. The specificity of action of MK-801 is supported by the finding that MK-801 strongly inhibited the binding of (+)-N-[3H]allylnormetazocine ((+)-[3H]SKF 10,047) to the PCP/sigma-receptor but its effect on (+)-[3H]SKF 10,047 binding to the non-PCP, haloperidol-sensitive sigma-binding site was weaker by several orders of magnitude. Furthermore, MK-801 exerts PCP-like antagonistic effects upon NMDA-induced [3H]norepinephrine release. These findings support the concept that the anticonvulsant and anti-NMDA effects of MK-801 result from its being the most potent known ligand of PCP/sigma-receptors.
...
PMID:The novel anticonvulsant MK-801: a potent and specific ligand of the brain phencyclidine/sigma-receptor. 282 53

1-[1-(3-Hydroxyphenyl)cyclohexyl]piperidine (PCP-3-OH) is one of the most potent analogs of phencyclidine (PCP). In the present study we describe the binding properties of 3H-PCP-3-OH to guinea pig brain membranes. Scatchard analysis of saturation binding studies revealed the existence of high (0.44nM) and low (17nM) affinity binding components. High affinity binding sites were completely blocked in the presence of (+)SKF 10047 (50nM). In competition studies PCP analogs compete for 3H-PCP-3-OH specific binding in a monophasic manner whereas psychotomimetic opioid ligands compete for this binding in a biphasic manner. Results from both saturation and competition experiments suggest the existence of a common high affinity binding site for psychotomimetic opioid ligands and PCP analogs and a low affinity binding component primarily for phencyclidines.
...
PMID:High and low affinity psychotomimetic opioid binding sites: characterization by a novel 3H-PCP-analog. 282 67

The effect of guanine nucleotides and ions on (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+ )-[3H]3-PPP), (+)-N-[3H]allylnormetazocine ((+)-[3H]SKF 10047) and [3H]1-[1-(3-hydroxyphenyl)-cyclohexyl]piperidine ([3H]PCP-3-OH) specific binding to rat brain membranes was examined. These 3 compounds are proposed as prototypical ligands for the labeling of the sigma- and phencyclidine (PCP)-receptor subtypes. Competition binding experiments of (+)-SKF 10047 with (+)-[3H]3-PPP yielded a biphasic inhibition curve which transformed to a monophasic curve when membranes were incubated in the presence of Gpp(NH)p (0.1 mM). The common (+)-[3H]3-PPP/(+)-SKF 10047 binding component is more susceptible to Gpp(NH)p than the high affinity [3H]PCP-3-OH/(+)-SKF 10047 common binding component. Low affinity [3H]PCP-3-OH binding, which may represent a PCP-selective site, is not affected by GTP and Gpp(NH)p. Mono- and divalent cations markedly inhibit high affinity [3H]PCP-3-OH binding but they had a differential inhibitory effect on the binding of the other radioligands tested. These findings suggest differences in the regulation of multiple psychotomimetic (sigma- and PCP) binding sites by guanine nucleotides and ions.
...
PMID:Regulation of the binding of sigma- and phencyclidine (PCP)-receptor ligands in rat brain membranes by guanine nucleotides and ions. 283 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---