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 profile of action of eptazocine, a novel analgesic, on opioid receptors was investigated. Eptazocine caused a concentration-dependent inhibition against the [3H]-naloxone [( 3H]-NLX) specific binding to rat brain synaptic membrane in the absence of sodium cation and GTP (IC50; 7.83 +/- 1.57 microM). The ratios of IC50 values between the absence to the presence of sodium cation alone or sodium cation and GTP were 3.89 and 4.35, respectively. In addition, eptazocine (10 microM) also produced the significant decrease of [3H]-NLX specific binding in the mouse brain synaptic membrane. Moreover, the same dose eptazocine significantly decreased the [3H]-ethylketocyclazocine [( 3H]EKC) specific binding, but not [3H]-phencyclidine [( 3H]-PCP). These results suggest that eptazocine interacts with opioid receptor, and is classified as one of the opiate agonist-antagonist analgesics.
 ...
PMID:The interaction of eptazocine, a novel analgesic, with opioid receptors. 299 58

An urban terrestrial microecosystem has been used under outdoor conditions to study the transfer of chemical residues within the system components. The microecosystem consisted of soil monoliths obtained from a site with an established vegetation cover dominated by goldenrod, Solidago gigantea. The microecosystem contained integrated food chain elements composed of primary producers, herbivores and carnivores. The system was stocked with indicator insect species, snails (Cepaea nemoralis) and earthworms (Allolobophora caliginosa), captured from the original site. Evaluation of the system was made using radiolabelled sodium pentachlorophenate (PCP-Na) which was applied as a single application at an equivalent rate of 5 kg ha-1. The mass balance revealed that, after 131 days, in the autumn, and after 222 days, in the winter, that 43 and 39% radiocarbon, respectively, was recoverable from the microecosystem. The unaccounted radiocarbon was very probably removed through volatilization and photomineralization of the compound. PCP residues on foliage decreased rapidly, 50% of which were metabolised within 15 days. Most of the radiocarbon remaining in the system after 131 days was in the top soil and plant litter, transmitted mainly through washing off by rain and leaf litter fall. There was a variation in the uptake of PCP-Na residues in the food chain organisms, where the total radiocarbon concentrations during the first 19 days of exposure ranged, e.g. in snails, from 3 to 0.6 micrograms g-1, in springtails from 5 to 105; in beetles (Amara fusca) from 3 to 1, in spiders from 13 to 11, and in harvestman from 31 to 77 micrograms g-1. The ecological magnification indices (EM) of all the organisms with respect to their main food source, i.e. plant litter, demonstrated no bioconcentration effects. This is attributed to the metabolism of PCP-Na by the organisms and its rapid excretion. The urban wasteland ecosystem contained in outdoor lysimeters employed as a model gives valuable information and has considerable value in predicting the ecological fate of industrial chemicals.
 ...
PMID:Environmental fate and distribution of sodium [14C] pentachlorophenate in a section of urban wasteland ecosystem. 336 14

A benzothiophenyl group instead of a phenyl ring on phencyclidine (PCP) yields a molecule N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), which is one of the more potent known dopamine (DA) uptake inhibitors (IC50 = 7 nM). This compound also has low affinity for the PCP receptor (K0.5 = 6 microM). The sodium-dependent [3H]BTCP binding to rat striatal membranes was investigated. [3H]BTCP bound to two different sites: one with very high affinity (Kd1 = 0.9 nM, Bmax1 = 3.5 pmol/mg protein) which paralleled the distribution of dopaminergic nerve endings and a second with lower affinity (Kd2 = 20 nM, Bmax2 = 7.5 pmol/mg protein). There was a good correlation between the abilities of drugs specific for the DA uptake complex and of PCP analogs to inhibit high affinity [3H]BTCP binding and [3H]DA synaptosomal uptake. This study also demonstrated that PCP interacts with the DA uptake site since it is a competitive inhibitor of high affinity [3H]BTCP binding. This site, however, is not the PCP receptor, which has a different pharmacological selectivity.
 ...
PMID:[3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex. 338 5

We studied the effects of phencyclidine (PCP) on voltage-dependent K+ currents in cultured embryonic rat hippocampal neurons. Whole cell voltage-clamp recordings were made in the presence of tetrodotoxin to block Na+ current. Depolarizing voltage steps activated two outward current components: (i) a rapidly activating and inactivating ('transient') component, IA, and (ii) a slowly activating, minimally inactivating ('sustained'), component, IK. At low concentrations (less than 50-100 microM), PCP produced a selective, reversible blockade of IK with minimal effect on IA; however, at higher concentrations both currents were suppressed. The IC50's for blockade of IK and IA were 36 and 310 microM, respectively.
 ...
PMID:Phencyclidine at low concentrations selectively blocks the sustained but not the transient voltage-dependent potassium current in cultured hippocampal neurons. 338 79

Brown oxidation of cis-bicyclo[3.1.0]hexan-3-ol afforded bicyclo[3.1.0]hexan-3-one in 98% yield. Treatment of this ketone with either phenyllithium or phenylamagnesium bromide in ether at room temperature followed by solvolysis of the resulting alcohol in a mixture of trifluoroacetic acid, sodium azide, and chloroform gave a mixture of cis- and trans-3-azido-3-phenylbicyclo[3.1.0]hexanes. LAH reduction of this crude mixture of azides afforded a 1:3.5 mixture of cis- and trans-3-phenyl-3-bicyclo[3.1.0]hexylamine, respectively, in 51% overall yield from the alcohol. Separation of the mixture of amines by column chromatography followed by cyclization of each by heating at 60 degrees C in DMF solution with 1 equiv of 1,5-dibromopentane furnished the two conformationally restrained analogues of phencyclidine (PCP), cis- and trans-3-phenyl-3-piperidinylbicyclo[3.1.0]hexane (1 and 2, respectively), in high yield. Configurations were assigned on the basis of an X-ray crystallographic analysis of the cis isomer (1). Bond lengths and angles are similar to those found in PCP and its derivatives. Binding to PCP receptors and sigma sites as well as behavioral effects of 1 and 2 in rats was determined relative to PCP. In displacement of specifically bound [3H]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP receptors, 1 and 2 were nearly equipotent and about one-seventh as potent as PCP. These compounds were about one-fifth as potent as PCP in displacing [3H]-(+)-SKF 10,047 from its binding site. Calculation of the ED50 values of 1 and 2 for stereotyped behavior and ataxia indicated that they were about equipotent, and 2-3-fold less active than PCP.
 ...
PMID:Synthesis, configuration, and evaluation of two conformationally restrained analogues of phencyclidine. 339 94

The effect of trifluoperazine (TFP) and phencyclidine (PCP) on acetylcholine receptor (AChR) function was studied in rat muscles differentiated in cell culture. While both drugs exerted an inhibitory effect on carbamylcholine (CCh)-induced Na+ or Ca2+ influx (I50 = 5-7 microM), alpha-bungarotoxin binding was not affected. The inhibitory effect of both drugs was independent of CCh concentration, which deems it unlikely that these drugs enhanced desensitization. The mutual inhibitory effect of TFP and PCP on Ca2+ influx was analyzed using three alternative models of interaction between the two drugs: competitive, additive and synergistic inhibition models. Our results are in accordance with a synergistic interaction between the drugs. This synergistic interaction between the drugs provides a biochemical rationale to the phenothiazine contraindication in the treatment of PCP psychosis.
 ...
PMID:Trifluoperazine and phencyclidine inhibit synergistically carbamylcholine-induced cation influx in muscle cultures. 343 92

The effect of trifluoperazine (TFP) and phencyclidine (PCP) on acetylcholine receptor (AChR) function was studied in rat myotubes differentiated in vitro. While both drugs exerted an inhibitory effect on carbamylcholine (CCh)-induced Na+ or Ca2+ flux (I50 = 5-9 microM), alpha-bungarotoxin (alpha-Bgt) binding was not affected. The inhibitory effect of both drugs was independent of CCh concentration. The mutual inhibitory effect of TFP and PCP on Ca2+ influx was analyzed using three alternative models of interaction between the two drugs: competitive, additive and synergistic inhibition models. Our results are in accord with a synergistic interaction between the drugs probably not through desensitization. This synergistic interaction between the drugs provides a biochemical rationale to the phenothiazine contraindication in the treatment of PCP psychosis.
 ...
PMID:Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures. 360 41

The hypothesis that the ADP-sensitive form of phosphorylated Na+, K+-ATPase contains occluded sodium ions has been tested by a procedure which involves (i) modifying the enzyme with alpha-chymotrypsin or N-ethylmaleimide (NEM) so that the ADP-sensitive form is more stable than it is in the native enzyme, (ii) phosphorylating the modified enzyme with ATP in the presence of labelled sodium ions, and (iii) forcing the phosphorylated enzyme rapidly through a cation-exchange column and measuring the labelled sodium in the effluent. The results show that ADP-sensitive phosphoenzyme prepared from alpha-chymotrypsin- or NEM-modified Na+, K+-ATPase is able to carry labelled sodium ions through a cation-exchange resin. This behaviour was not seen with native Na+, K+-ATPase or when phosphorylation was prevented by the omission of magnesium ions or by the substitution of adenylyl(beta, gamma-methylene)diphosphonate (AMP-PCP) for ATP. The occluded sodium ions were rapidly released when the phosphoenzyme was dephosphorylated by ADP. When alpha-chymotrypsin-modified enzyme was phosphorylated by ATP with 1 mM-sodium in the medium, close to three sodium ions were occluded per phospho group. The stoicheiometry at much lower sodium concentrations could not be determined satisfactorily. A consideration of the rate constants of the reactions thought to be involved in the occlusion of sodium and in the release of sodium from the occluded state shows that, so far as they are known, these constants are compatible with the hypothesis that the occluded-sodium form of the phosphoenzyme plays a central role in sodium transport through the pump.
 ...
PMID:The occlusion of sodium ions within the mammalian sodium-potassium pump: its role in sodium transport. 608 5

1. Changes in the intrinsic fluorescence of Na, K-ATPase protein have been used to monitor the interconversion of E(1) (low fluorescence) and E(2) (high fluorescence) forms of the unphosphorylated enzyme.2. In media lacking sodium and nucleotides, 1 mM-potassium was sufficient to convert practically all of the enzyme into the E(2) form. In media containing 1 mM-potassium, 1 mM-EDTA, and no sodium or magnesium, the addition of ATP, or its beta, gamma-imido or methylene analogues, converted the enzyme back into the E(1) form. The relation between nucleotide concentration and the fraction of the enzyme that was in the E(1) form could be described by a rectangular hyperbola, with a K((1/2)) of about 15 muM for ATP, 65 muM for adenylyl-imidodiphosphate (AMP-PNP) and 180 muM for adenylyl (beta, gamma-methylene)-diphosphonate (AMP-PCP). ADP also converted the enzyme back into the E(1) form, with a K((1/2)) of about 25 muM, but the relation between concentration and fraction converted was not well described by a rectangular hyperbola.3. In similar media containing 50 mM-potassium, much higher concentrations of ATP were required to convert the enzyme back into the E(1) form, and the conversion was probably incomplete.4. If we assume that ATP and potassium ions affect each other's binding solely by altering the equilibrium between E(1) and E(2) forms of the enzyme, we are able to conclude (i) that potassium ions bind to the E(1) form with a moderately low affinity, (ii) that, in the absence of nucleotides, the equilibrium between E(1)K and E(2)K is poised strongly in favour of E(2)K, (iii) that the binding of ATP to a low-affinity site alters the equilibrium constant for the interconversion of E(1)K and E(2)K by two to three orders of magnitude, so that, at saturating levels of ATP, the equilibrium is probably slightly in favour of E(1)K, and (iv) that in sodium-free, potassium-containing media, ATP will appear to bind to the enzyme more tightly than would be expected from the dissociation constant of the E(2)K. ATP complex.5. The pattern of the equilibrium constants for the various reactions between E(1), E(2), ATP and potassium is compatible with the hypothesis that the ATP-accelerated conversion of E(2)K into E(1)K, and the subsequent release of potassium ions from low-affinity inward-facing sites, are part of the normal sequence of events during potassium influx in physiological conditions.
 ...
PMID:The equilibrium between different conformations of the unphosphorylated sodium pump: effects of ATP and of potassium ions, and their relevance to potassium transport. 624 81

[3H]Phencyclidine (PCP) binds to a single class of noninteracting binding sites in rat brain membranes with an affinity Kd of 0.25 microM and a maximal binding capacity BM of 2.4 pmol/mg of membrane protein. PCP derivatives also interact with the muscarinic and mu-opiate receptors in rat brain membranes with affinities that are one or two orders of magnitude lower than those observed for the [3H]PCP-binding sites. Activities of 25 PCP derivatives in the rotarod assay are closely correlated to affinities of these molecules for the [3H]PCP-binding sites, but not for the muscarinic or mu-opiate receptors. Monohydroxylation of PCP generally decreases the affinity of PCP for the [3H]PCP- and muscarinic-binding sites and does not change the affinity for the mu-opiate receptor. The metaphenolic derivative of PCP does not follow these general rules; the affinities of this derivative for the [3H]PCP- and mu-opiate-binding sites are 8 and 430 times higher, respectively, than those of PCP itself. Voltage-clamp experiments with N1E 115 neuroblastoma cells show that PCP is an efficient blocker of both the K+ channel (EC50 = 2.6 microM) and the Na+ channel (EC50 = 9.2 microM).
 ...
PMID:Identification and properties of phencyclidine-binding sites in nervous tissues. 630 60


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