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)

T lymphocyte-mediated immunity is important for resistance to Francisella tularensis. To characterize the specificity of this immunity, we used membrane proteins and two lipopolysaccharide (LPS) preparations. Both membrane proteins were heat-modifiable, as indicated by their migration in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). One had an apparent molecular mass (Mm) of 120 kilodaltons (kDa) when solubilized in the SDS buffer at room temperature, but 17 kDa after heating. The respective values for the other protein were 35 kDa before and 40 kDa after heating. Both proteins were purified by a preparative SDS-PAGE. The LPS-containing preparations were isolated by aqueous phenol (WP) or PCP (phenol-chloroform-petroleum ether) extraction (LPS-R), and rendered protein-free by treatment with proteinase K. Lymphocytes from nine subjects immunized with a live tularemia vaccine from one to three years earlier responded specifically to both an F. tularensis whole cell antigen and the 17 kDa protein in the lymphocyte blast transformation test. By contrast, the 40 kDa protein and the two LPS preparations did not stimulate any detectable lymphocyte proliferation.
Microb Pathog 1989 Dec
PMID:Membrane proteins of Francisella tularensis LVS differ in ability to induce proliferation of lymphocytes from tularemia-vaccinated individuals. 262 30

Twelve children with laboratory evidence of human immunodeficiency virus (HIV) infection underwent diagnostic flexible bronchoscopy with washings or bronchoalveolar lavage at Bellevue Hospital Center from October 1987 to April 1989. The patients included 7 boys and 5 girls ranging from age 3.5 months to 10 years 5 months. Indications for bronchoscopy included respiratory distress with or without focal changes on chest radiograph in 11 patients, and persistent but asymptomatic right middle lobe collapse in one child. The etiology of pneumonia was diagnosed in 7 children and included Pneumocystis carinii, (PCP) (17%), Streptococcus viridans (17%), mechanical obstruction (17%) and cytomegalovirus (CMV) (8%). Bronchoscopy was non-diagnostic in 5 cases. Techniques for maximal yield of information using flexible bronchoscopy in HIV-positive children are discussed.
Int J Pediatr Otorhinolaryngol 1989 Dec
PMID:Diagnostic flexible bronchoscopy in human immunodeficiency virus (HIV)-positive children. 262 88

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.
Endocrinology 1987 Dec
PMID:Receptors and secretory actions of sigma/phencyclidine agonists in anterior pituitary cells. 282 79

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
J Pharmacol Exp Ther 1987 Dec
PMID:Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats. 282 56

The phencyclidine (PCP) receptor acylator, metaphit, has been reported to act as a PCP antagonist. Recent electrophysiological and behavioral assessments of metaphit action have revealed, however, that this compound can also act as a PCP-like agonist. The present study examined the effects of metaphit on the inhibition of N-methyl-D-aspartate (NMDA)-induced 3H-acetylcholine (ACh) release, 3H-TCP binding and synaptosomal 3H-dopamine (DA) uptake in the rat striatum. Preincubation of striatal slices for 10 min in the presence of metaphit, followed by a prolonged washout, produced a concentration-dependent inhibition of the ACh release evoked by 300 microM NMDA. At high concentrations, preincubation with PCP also resulted in inhibition of this measure. However, this could be reduced by extending the washout period, a procedure which had no effect on the inhibition produced by metaphit. At 10 microM, metaphit resulted in a 53% reduction in NMDA-evoked ACh release while PCP had no effect under identical conditions. Preincubation of slices in 10 microM PCP and metaphit reduced the metaphit inhibition by 62%. The effects of PCP and metaphit, alone or in combination, on NMDA-induced ACh release were paralleled by a loss of 3H-TCP binding sites in striatal tissue incubated under identical conditions suggesting that metaphit exerts long-lasting agonist-like actions on PCP receptors coupled to NMDA receptors. Although these results do not explain the ability of metaphit to antagonize PCP effects in other assays, we did observe that preincubation of striatal synaptosomes with metaphit also resulted in an irreversible inhibition of 3H-DA uptake. These data are discussed in relation to the interaction of metaphit with PCP receptors in various systems.
Life Sci 1987 Dec 14
PMID:Phencyclidine (PCP)-like inhibition of N-methyl-D-aspartate-evoked striatal acetylcholine release, H-TCP binding and synaptosomal dopamine uptake by metaphit, a proposed PCP receptor acylator. 282 48

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.
Brain Res 1987 Dec 01
PMID:The novel anticonvulsant MK-801: a potent and specific ligand of the brain phencyclidine/sigma-receptor. 282 53

Computer-assisted molecular modelling techniques have been employed to develop receptor models for the phencyclidine (PCP) and sigma binding sites. The models differ in the position of the nitrogen atom, direction of the nitrogen-lone pair vector and in the location and nature of secondary binding groups. This study predicts the existence of distinct receptors for sigma and PCP ligands, and our receptor models can be used to design and predict the activity of drugs with PCP and/or sigma activity.
Eur J Pharmacol 1987 Dec 01
PMID:Quantitative conformational analyses predict distinct receptor sites for PCP-like and sigma drugs. 283 Jan 25

Computer-assisted molecular modelling techniques and electrostatic analyses of a wide range of phenycyclidine (PCP) and sigma ligands, in conjunction with radioreceptor studies, were used to determine the topographies of the PCP and sigma receptors. The PCP receptor model was defined using key molecules from the arylcyclohexylamine, benzomorphan, bridged benz[f]isoquinoline, and dibenzocycloalkenimine drug classes. Hypothetical receptor points (R1, R2) were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor, along with an additional receptor point (R3) representing a hydrogen bond between the nitrogen atom and the receptor. The superimposition of these key molecules gave the coordinates of the receptor points and nitrogen defining the primary PCP pharmacophore as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.66, -1.13, 0.00), and N (3.90, -1.46, -0.32). Additional analyses were used to describe secondary binding sites for an additional hydrogen bonding site and two lipophilic clefts. Similarly, the sigma receptor model was constructed from ligands of the benzomorphan, octahydrobenzo[f]quinoline, phenylpiperidine, and diphenylguanidine drug classes. Coordinates for the primary sigma pharmacophore are as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.09, 2.09, 0.00), and N (4.9, -0.12, -1.25). Secondary binding sites for sigma ligands were proposed for the interaction of aromatic ring substituents and large N-substituted lipophilic groups with the receptor. The sigma receptor model differs from the PCP model in the position of nitrogen atom, direction of the nitrogen lone pair vector, and secondary sigma binding sites. This study has thus demonstrated that the differing quantitative structure-activity relationships of PCP and sigma ligands allow the definition of discrete receptors. These models may be used in conjunction with rational drug design techniques to design novel PCP and sigma ligands of high selectivity and potency.
Mol Pharmacol 1988 Dec
PMID:Receptor site topographies for phencyclidine-like and sigma drugs: predictions from quantitative conformational, electrostatic potential, and radioreceptor analyses. 284 51

Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [3H]haloperidol or 1,3 di(2-([5-3H]tolyl)guanidine ([3H]DTG) to specifically label sigma receptors and 3,4-[3H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) to specifically label PCP receptors. [3H]Haloperidol binding was saturable and of high affinity with comparable KD values in human PBL (0.44 +/- 0.10 nM) and rat cerebellum (0.51 +/- 0.09 nM). Similarly, [3H]DTG binding was saturable with comparable KD values of 29.5 +/- 3.5 and 26.4 +/- 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [3H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [3H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol greater than l-butaclamol = pentazocine greater than d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine greater than DTG = d-butaclamol = d-SKF 10,047 greater than levallorphan greater than or equal to PCP greater than or equal to l-SKF 10,047 greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1988 Dec
PMID:Initial identification and characterization of sigma receptors on human peripheral blood leukocytes. 284 60

Research on the sigma receptor, a binding site associated with drug-induced psychotomimetic behaviors, has been hampered because most sigma agonists also interact with the phencyclidine (PCP) receptor. (+)-Pentazocine, a human psychotogen, is a selective sigma receptor ligand. To demonstrate sigma receptor activities, we studied the behavioral and electrophysiologic actions for (+)-pentazocine. In the behavioral drug discrimination procedure in which rats were trained to discriminate between 2.0 mg/kg (5.59 mumol/kg) (+)-pentazocine and saline, (+)-pentazocine produced dose-related increases in the percentage of trials completed on the (+)-pentazocine lever. At a dose of 1.0 mg/kg (3.29 mumol/kg) (+)-N-allylnormetazocine generalized completely to (+)-pentazocine. By contrast, PCP only partially generalized. In the visual evoked potential test, these compounds produced a significant dose-dependent slowing of the N2 latency. This response was prevented by haloperidol pretreatment. These results demonstrate pharmacologic actions for the selective sigma receptor ligand (+)-pentazocine and suggest some overlapping pharmacologic properties of the sigma and PCP receptor sites despite differences in central nervous system distribution.
Neuropsychopharmacology 1988 Dec
PMID:Biochemical, behavioral, and electrophysiologic actions of the selective sigma receptor ligand (+)-pentazocine. 285 2


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