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)

Adult mice were exposed to long-term phencyclidine (PCP) treatments as animal models for psychosis. The drug was administered via osmotic minipumps implanted subcutaneously in the backs of the mice. The treatments for 7 days with 2.5 and 1 mg/d/mouse and the treatment for 3 days with 1 mg/d/mouse differentially affected the release of dopamine and D-aspartate from striatal and frontal cortical slices. In frontal cortical slices the potassium-stimulated release of dopamine increased, whereas the release of D-aspartate varied with the PCP dose. In striatal slices the release of D-aspartate was either decreased or unchanged, whereas the release of dopamine was mostly unchanged. The 3-day treatment with PCP followed by the 3-day period of withdrawal increased the potassium-stimulated release of dopamine from frontal cortical slices and decreased that from striatal slices. In brain slices from untreated mice PCP increased the release of dopamine in vitro, whereas the release of D-aspartate was not affected. It seems that PCP has region-specific effects on both dopaminergic and glutamatergic transmission in the central nervous system, and it may thus serve as an interesting experimental model for further research on psychosis.
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PMID:Phencyclidine treatments differentially affect dopamine and D-aspartate release from frontal cortical and striatal slices from mice. 134 50

Tris-HCl is the most commonly used buffer in studies of radioligand binding to sigma receptors, with concentrations as high as 50 or 100 mM often used. We report here that these concentrations of Tris substantially inhibit (+)-[3H]SKF-10,047 binding to sigma receptors. The well-established inhibitory effect of Tris-HCl on ligand binding to PCP receptors did not contribute to the presently reported inhibition of (+)-[3H]SKF-10,047 binding. The IC50 of Tris, determined in the presence of 10 mM potassium phosphate buffer, was 15.4 +/- 1.2 mM (n = 3, pH 8.0, 25 degrees C, 1 nM radioligand). Equilibrium saturation studies revealed an apparent competitive inhibition of binding.
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PMID:Tris inhibits (+)-[3H]SKF-10,047 binding to sigma receptors. 143 40

The sigma receptor is a neuronal substrate that binds several psychoactive compounds. These include cocaine, some steroids, dextromethorphan, phencyclidine (PCP), and benzomorphans such as pentazocine and N-allyl-normatezocine (SKF-10047). Many newer atypical antipsychotic drugs also bind to the sigma receptor. The sigma receptor, however, is not the PCP receptor. The sigma receptor exists in the central nervous system, endocrine, immune and certain peripheral tissues. Progesterone and certain steroids have been shown to represent endogenous ligands for the sigma receptor. The sigma receptor resides likely in the nonsynaptic region of the plasma membrane. The sigma receptor exists in two forms: high-affinity and low-affinity. The solubilized sigma receptor retains all of the pharmacological characteristics of a membrane-bound receptor. A major physiological role of the sigma receptor may involve the modulation of a tonic potassium channel.
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PMID:Sigma receptors. Putative links between nervous, endocrine and immune systems. 165 24

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 ability to alter immunoassay test results by the addition of some commonly available chemicals to drug-positive and drug-negative urine specimens was investigated. Urine specimens containing either phencyclidine (PCP) or 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) were adulterated with sodium chloride, bleach, vinegar, potassium hydroxide, liquid soap, 2-propanol, and ammonia. Subsequent analyses by radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) demonstrated false positive and false negative results with some adulterants. Radioimmunoassay false positives occurred with potassium hydroxide (PCP and THC-COOH assays) and bleach (THC-COOH assay) adulterants. Bleach (PCP assay) and soap (THC-COOH assay) additives resulted in false negative analyses by RIA. No adulterant caused FPIA false positives. FPIA false negatives occurred with bleach (PCP and THC-COOH assays) and potassium hydroxide (PCP assay) adulterants.
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PMID:Detectability of phencyclidine and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in adulterated urine by radioimmunoassay and fluorescence polarization immunoassay. 196 89

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 microM - 10 mM), PCP increased the width of action potentials (APs). Doses of 10 microM and higher were associated with decreased action potential amplitude. PCP decreased inhibitory postsynaptic potentials and excitatory postsynaptic potentials but did not alter responses to focally applied GABA. At the lowest dose (0.2 microM), PCP decreased the input resistance (Rin), while at all other doses Rin was increased. PCP decreased post-spike train afterhyperpolarizations at low and medium doses. PCP effects persisted in low calcium medium and also in medium containing 10(-6) M tetrodotoxin. It is concluded that in these central neurons, PCP primarily blocks potassium conductances at all doses and, at anesthetic doses, depresses sodium-dependent spikes.
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PMID:Phencyclidine actions measured intracellularly in hippocampal CA1 neurons. 207 27

Potassium-evoked release of cholecystokinin (CCK) from slices of caudate-putamen, hippocampus, and cerebral cortex was inhibited in a dose-related fashion by phencyclidine (PCP). In order to further examine this effect, PCP-like ligands (dexoxadrol, levoxadrol, PCMP and MK-801) as well as compounds known to interact with the sigma receptor ((+)-SKF, DTG, (+)-3-PPP, and pentazocine) were tested. While some of these compounds inhibited CCK release, their rank order potency (Dex = Lev greater than PCP = PCMP greater than DTG = MK-801 = (+)-3-PPP) differs from that of known PCP-N-methyl-D-aspartate linked effects or sigma interactions. These results suggest that the mechanism by which PCP acts to inhibit CCK release may involve a novel type of PCP interaction.
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PMID:Inhibition of potassium-evoked release of cholecystokinin from rat caudate-putamen, cerebral cortex and hippocampus incubated in vitro by phencyclidine and related compounds. 217 16

The present review deals with the molecular mechanisms and elementary phenomena underlying the activation of the voltage- and chemo-sensitive membrane macromolecules: sodium- and potassium-ion channels and nicotinic ACh receptors and their associated ion channel. To achieve an understanding of their various kinetics and conformational states, a number of novel alkaloids, BTX, HTXs, gephyrotoxins, and certain psychotomimetic drugs such as phencyclidine, and many other pharmacologically active agents have been used. Biochemical assays and various electrophysiological techniques have been used in a number of biological preparations--e.g., Torpedo membranes, brain synaptosomes, amphibian and mammalian neuromuscular preparations--to describe the action of such agents. The availability of BTX and scorpion toxins together with aconitine and veratridine as activators and TTX and STX as antagonists of the voltage-sensitive sodium channels, made possible the identification and the physiological and pharmacological characterization of these channels. These studies provided the basis for understanding the mechanisms underlying electrical excitability and culminated, more recently, in the purification and reconstitution of sodium channels from rat brain and in the successful cloning of these channels with the elucidation of their primary structure. We now know that the sodium channel has a molecular mass of 316,000 daltons, consists of five subunits, and has multiple sites for various ligands. In contrast to sodium channels, various classes of potassium channels (inward and outward rectifier potassium channels and Ca(2+)-activated potassium channels) have been described. Unlike the sodium channels, there are no known specific activators for potassium channels. However, a number of potassium channel blockers such as 4-aminopyridine, HTX, histamine, and norepinephrine have been identified which complement the varying types of potassium channels in different neurons. One class of potassium channel blockers with profound medical and social implications comprises PCP and its analogues. The blockade of the potassium-induced 86Rb+ efflux from brain cells, the resulting prolongation of muscle and nerve action potentials, and the increase in transmitter release observed with PCP and some analogues are all highly suggestive of a role for the potassium channel in the behavioral effects of these drugs and its potential involvement in schizophrenia. A number of toxic principles of both plant and animal origin played a significant role in the development of our knowledge about the nAChR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Macromolecular sites for specific neurotoxins and drugs on chemosensitive synapses and electrical excitation in biological membranes. 248 4

Large concentrations of potassium were used to stimulate the release of rubidium-86 from preloaded cortical synaptosomes, so that the pharmacological sensitivity of this efflux could be examined. Potassium channel blockers, 4-aminopyridine and tetraethylammonium, inhibited the evoked release of rubidium. Sigma ligands, e.g. pentazocine, cyclazocine, rimcazole, 1,3-di(2-tolyl)guanidine (DTG) and haloperidol, as well as the antitussives, carbetapentane, caramiphen and dextromethorphan, significantly reduced potassium-stimulated efflux of rubidium. By contrast, 3-hydroxyphenyl-propylpiperidine (3-PPP), 5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK-801), phencyclidine (PCP), ketamine and D-2-amino-5-phosphonovalerate (D-AP5) were all inactive. This suggests that inhibition of potassium-stimulated efflux of rubidium is correlated with activity at the sigma and/or dextromethorphan binding sites rather than at the N-methyl-D-aspartate (NMDA)/PCP receptor-channel complex.
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PMID:Efflux of rubidium in rat cortical synaptosomes is blocked by sigma and dextromethorphan binding site ligands. 254 9

The patch-clamp open-cell recording configuration has been used to investigate the effects of non-hydrolyzable analogues of ATP on the diazoxide-activation of KATP channels in the insulin-secreting cell line RINm5F. K+ channels inhibited by 0.1, 0.5 and 1.0 mM ATP were consistently activated by 200 microM diazoxide. During sustained activation of channels, exchange of ATP for either AMP-PNP, AMP-PCP or ATP gamma S abolished the effects of diazoxide. If diazoxide was added to the membrane in the continued presence of AMP-PNP, AMP-PCP or ATP gamma S either no effects were observed or alternatively a small transient activation of channels occurred. This study suggests that protein phosphorylation is necessary for diazoxide to activate ATP-sensitive potassium channels in insulin-secreting cells.
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PMID:Protein phosphorylation is required for diazoxide to open ATP-sensitive potassium channels in insulin (RINm5F) secreting cells. 266 56


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