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)

Isolated sarcotubular membranes (SR) from skeletal muscle bound 3.7 nmol of beta, gamma-methylene [8-3H]ATP (AMP-PCP) per mg of membrane protein. Only one class of binding site was identified and the dissociation constant (K) for this site was 1.5 X 10(-5) M. Addition of 0.05% Triton X-100 increased the number of binding sites to 5.7 nmol/mg. ATP and ADP competitively inhibited AMP-PCP binding. The dissociation constants for ATP and ADP were 3.5 X 10(-5) M and 3.3 X 10(-6) M, respectively. Since this data was obtained in the presence of 5 mM EDTA, it was established that the sarcoplasmic reticulum has a high affinity for the metal free forms of ATP, ADP, and AMP-PCP. Magnesium concentrations in excess of 1 X 10(-4) M inhibited AMP-PCP binding. Lower concentrations of magnesium had little effect on AMP-PCP binding. The effect of calcium on AMP-PCP binding was biphasic. Calcium concentration between 1 X 10(-6) and 1 X 10(-4) M inhibited AMP-PCP binding. Inhibition was maximal at 1 X 10(-5) M. Calcium concentration above 1 X 10(-4) M facilitated analogue binding. Possible sites of magnesium and calcium actions are discussed.
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PMID:Effect of calcium and magnesium on binding of beta, gamma-methylene ATP to sarcoplasmic reticulum. 86 83

Phencyclidine (PCP) receptors have been solubilized from rat forebrain membranes with the zwitterionic detergent 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate. Specific binding of the potent PCP receptor ligands [3H]thienyl-phencyclidine (TCP) and [3H]MK-801 was restored by incorporating extracted membrane protein into lipid vesicles prepared from a total brain lipid extract. A nearly quantitative recovery of solubilized receptor activity was achieved; this was dependent upon both the concentration of detergent used during membrane solubilization and the concentration of added lipid used during the reconstitution. The single, saturable, binding site measured for both [3H]TCP and [3H]MK-801 in solubilized and reconstituted preparations exhibited properties similar to those of the high affinity PCP binding site labeled by these ligands in brain membranes. The ability of ligands selective for this site (MK-801, TCP, and dexoxadrol) to competitively displace specific [3H]TCP binding was retained after solubilization and reconstitution, although IC50 values measured for these ligands were shifted to higher concentrations. Levoxadrol and haloperidol were ineffective at displacing the radioligand binding in both membrane and vesicle preparations. The additive and dose-dependent ability of glutamate and glycine to enhance [3H]TCP binding to the solubilized/reconstituted receptor further suggests that a direct interaction with the N-methyl-D-aspartate receptor/ion channel complex has been preserved in the vesicle preparations. The photoaffinity labeling of two polypeptides (Mr 98,000 and 59,000) by azido-[3H]PCP was demonstrated in the vesicle preparations; this was largely prevented by competitive displacement of the radioligand with PCP before photolysis. These results establish both an essential lipid dependency and polypeptide composition for the high affinity, haloperidol-insensitive, PCP receptor in brain.
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PMID:High efficiency reconstitution of a phencyclidine/MK-801 receptor binding site solubilized from rat forebrain membranes. 165 3

Receptor binding studies with [3H]-(+)SKF-10047 were carried out to characterize the putative sigma (sigma) and phencyclidine (PCP) receptors in membrane preparations of bovine adrenal medulla. Specific binding of the radiolabelled compound was observed after incubation with the membrane preparation at 37 degrees, the equilibrium being reached at 20 min and the maximal binding being observed with 0.6 mg/ml protein. Saturation binding studies were performed at equilibrium (30 min at 37 degrees with 0.5 mg/ml of membrane protein) in the presence of haloperidol (1 microM) or 1-[1-(2-thienyl) cyclohexyl] piperidine (TCP; 0.2 microM) to block sigma or PCP receptors, respectively. The binding of [3H]-(+)SKF-10047 was characterized by two distinct components. A high affinity binding site (haloperidol sensitive) had an apparent KD of 8.3 nM and a Bmax of 67 pmol/g protein. A lower affinity binding site (TCP sensitive) had an apparent KD of 32.7 nM and a Bmax of 83 pmol/g protein. The drug specificity of the high affinity binding site resembled that of the putative sigma receptor, being potently inhibited by haloperidol and pentazocine. The binding pharmacology of the low affinity site resembled that of the phencyclidine receptor, being potently displaced by TCP and PCP. The binding of [3H]-(+)SKF-10047 to both receptors showed marked stereoselectivity for the dextrorotatory (+) isomer of SKF-10047 and was insensitive to the receptor specific opioid ligands DAGO (mu), DSLET (delta) and U-69593 (kappa). These data indicate that bovine adrenal medulla contains sigma and PCP-like receptors.
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PMID:Presence of sigma and phencyclidine (PCP)-like receptors in membrane preparations of bovine adrenal medulla. 254 82

[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).
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PMID:Identification and properties of phencyclidine-binding sites in nervous tissues. 630 60

(3H)-Phencyclidine (PCP) binds specifically to the cholinergic ionophore in synaptic membranes prepared from Torpedo electric organ. Experiments performed by the centrifugation method establish that the binding is saturable, reversible and selective and can be characterized by a single dissociation constant (3.6 +/- 1.8 microM). The maximal binding capacity is 600 +/- 150 pmol/mg of membrane protein. Bound (3H)-PCP can be displaced by unlabelled PCP and a series of its derivatives. The reactivity of PCP derivatives in binding to (3H)-PCP binding sites, as related to structural changes at the phenyl, piperidyl and cyclohexyl moieties, is discussed.
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PMID:Characterization of the interaction of phencyclidine and its derivatives with the ionic channel of the nicotinic receptor. 631 26

The effect of 6-ketocholestanol (kCh) on various natural and reconstituted membrane systems has been studied. 6-ketocholestanol (5 alpha-Cholestan-3 beta-ol-6-one), a compound increasing the membrane dipole potential, completely prevents or reverses the uncoupling action of low concentrations of the most potent artificial protonophore SF6847. This effect can be shown in the rat liver and heart muscle mitochondria, in the intact lymphocytes, in the Rhodobacter sphaeroides chromatophores, and in proteoliposomes with the heart muscle or Rh. sphaeroides cytochrome oxidase. The recoupling effect of kCh disappears within a few minutes after the kCh addition and cannot be observed at all at high SF6847 concentrations. Almost complete recoupling is also shown with FCCP, CCCP, CCP and platanetin. With 2,4-dinitrophenol, fatty acids and gramicidin, kCh is ineffective. With TTFB, PCP, dicoumarol, and zearalenone, low kCh concentrations are ineffective, whereas its high concentrations recouple but partially. The kCh recoupling is more pronounced in mitochondria, lymphocytes and proteoliposomes than in chromatophores. On the other hand, mitochondria, lymphocytes and proteoliposomes are much more sensitive to SF6847 than chromatophores. A measurable lowering of the electric resistance of a planar bilayer phospholipid membrane (BLM) are shown to occur at SF6847 concentrations which are even higher than in chromatophores. In BLMs, kCh not only fails to reverse the effect of SF6847, but even enhances the conductivity increase caused by this uncoupler. It is assumed that action of low concentrations of the SF6847-like uncouplers on coupling membranes involves cytochrome oxidase and perhaps some other membrane protein(s) as well. This involvement is inhibited by the asymmetric increase in the membrane dipole potential, caused by incorporation of kCh to the outer leaflet of the membrane.
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PMID:6-Ketocholestanol is a recoupler for mitochondria, chromatophores and cytochrome oxidase proteoliposomes. 903 Feb 61