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)

Evidence in this and other reports from this laboratory suggest that adrenergic nerves in rat heart ventricle slices incubated in a Na+-deprived (choline+) medium containing Ca++ (Ch+--Ca++), transport (by a cocaine-sensitive mechanism) 3H-norepinephrine outwardly from synaptic vesicles attached or fused to the plasma membrane. The 3H-amine secretion was not inhibited by probenecid, an anion transport inhibitor which may prevent exocytosis. The 3H-amine release was rapidly inhibited by exogenous nucleotides ATP, UTP, and GTP greater than ADP greater than AMP greater than the nucleoside adenosine. Magnesium++ tended to increase and reserpine to decrease the effect of ATP. Neither increasing the [Ca++] nor [Mg++] (to compete with Ca++ for ATP) decreased the effect of 3 mM ATP. After secretion began, lowering the Ca++ concentration by ommission, or by the inclusion of either a low concentration of EDTA or the Ca++-binding, but non-energy-conserving synthetic analogs of ATP: AMP--PCP and AMP--PNP, gradually lowered the rates of secretion. By comparison, the rapid effects of the energy-conserving nucleotides suggested that their effects were at least partially independent of chelation, and were energy dependent. ATP, unlike cocaine, did not inhibit the uptake of NE in a Krebs HCO3 medium. Inhibition of (Na+ + K+)-ATPase by ouabain neither inhibited the release by Ch+--Ca++, nor antagonizes the release inhibiting effect of ATP. Hence, ATP did not increase apparent retention of NE by stimulating the uptake of released NE. The ATP-inhibited secretion was not increased by theophylline.
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PMID:The effect of exogenous adenosinetriphosphate on the choline-calcium stimulated release of 3H-norepinephrine in rat heart ventricle slices. 668 77

The ability of phencyclidine (PCP), amphetamine and other substances to stimulate dopamine release from and inhibit dopamine uptake into rat striatal synaptosomes was examined in a continuous superfusion system. Inhibition of uptake was measured by determining inhibition of [3H]dopamine displacement by unlabeled dopamine ([1H]dopamine). The displacement of [3H]dopamine by 10(-7) M [1H]dopamine was temperature- and sodium-sensitive and calcium-independent. [1H]Dopamine was an order of magnitude more potent than serotonin or norepinephrine in displacing [3H]dopamine. The concentrations of reserpine required to inhibit [3H]dopamine uptake and [3H]dopamine displacement by [1H]dopamine were similar. Nomifensine, benztropine, PCP and amphetamine also inhibited the displacement of [3H]dopamine by [1H]dopamine at concentrations which have been shown previously to inhibit the uptake of [3H]dopamine, suggesting that the mechanism behind displacement and uptake are very similar. PCP, at 10(-7) to 10(-5) M, significantly inhibited [3H]dopamine displacement by 10(-7) M [1H]dopamine, PCP was less potent than nomifensine or benztropine in inhibiting [3H]-dopamine displacement by 10(-7) M [1H]dopamine, but was equipotent to amphetamine. Superfusion of the synaptosomes for 6 min with PCP, 10(-6)M, induced increases in the spontaneous release of dopamine. In this regard, PCP was less potent than amphetamine, reserpine, flupenthixol, or benztropine. Upon initial exposure of the synaptosomes to amphetamine at 10(-7) to 10(-5) M, a substantial calcium-dependent release of dopamine was induced. In contrast, PCP did not stimulate the early calcium-dependent release of dopamine. These results indicate that PCP is less potent than amphetamine at releasing dopamine and may affect dopamine metabolism in the striatum primarily by inhibiting the reuptake of this catecholamine.
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PMID:Effects of phencyclidine, amphetamine and related compounds on dopamine release from and uptake into striatal synaptosomes. 672 52

The myopathy induced in the rat by the central nervous system stimulant, phencyclidine (PCP), and restraint is characterized by extensive myofibrillar sarcomere disruption in hind limb muscles and massive increases in plasma creatine kinase (CPK) activity. The effects of dantrolene sodium on this myopathy were studied to determine if modulation of calcium release from the sarcoplasmic reticulum could alter the development of the myopathy. Dantrolene prevented both the sarcomere disruption and the increase in plasma CPK activity produced in the PCP-restraint model. The inhibitory effect was not due to a decrease in the locomotor activity produced by PCP. The findings are consistent with a role for excess sarcoplasmic calcium, originating from the sarcoplasmic reticulum, in the development of this myopathy.
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PMID:Retention of sarcoplasmic calcium inhibits development of the phencyclidine-restraint experimental myopathy. 682 47

The binding of phencyclidine to the acetylcholine receptor from Torpedo marmorata electroplaque was measured following solubilization of the receptor in sodium cholate followed by the exchange of cholate for Tween 80. In both the membrane-bound and solubilized AChR, the addition of cholinergic agonists simultaneously with the addition of PCP results in a 100 to 1000 fold increase in the PCP association rate and a 5 to 10 fold increase in the dissociation rate as compared to the unliganded AChR or AChR equilibrated with agonist prior to PCP addition. In addition, the number of binding sites and the pharmacological properties of the binding are not markedly changed in the soluble receptor. These results suggest that the acetylcholine receptor can undergo similar conformational transitions in the membrane-bound and the Tween 80 solubilized form and that phencyclidine can monitor these transitions in both cases.
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PMID:Binding of phencyclidine to the detergent solubilized acetylcholine receptor from Torpedo marmorata. 682 94

Effect of sublethal concentrations (0.0083, 0.0055, 0.0041, 0.0033 and 0.0028 mg/l) of sodium penta-chlorophenate (Na-PCP) on the enzymes SDH, PDH and LDH in brain, liver and gills of Notopterus notopterus after 15 ad 30 days exposure were studied. SDH and PDH were inhibited, and LDH were stimulated significantly at most concentrations. However, changes were maximum (-68.3%, -73.4% and +197.7% for SDH, PDH and LDH, respectively) in brain after 30 days, and minimum (-1.3% and +2.4% for SDH and LDH, respectively) in gills and (-3.4% for PDH) brain after 15 days. Inhibition of SDH and PDH, and the stimulation of LDH activity indicate the development of anaerobic conditions at the cellular level in pollutant-stressed fish.
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PMID:Effects of sodium pentachlorophenate on enzymes of energy metabolism in tissues of Notopterus notopterus. 708 Jan

Subeffective doses (0.5 mg) of 3H-phencyclidine (PCP) were given intravenously to three healthy men under two regimens designed to alkalinize or acidify their urine (oral sodium bicarbonate or ammonium chloride). The concentrations of PCP and its metabolites in saliva, plasma, and urine for 7 hr after injection were determined by high-performance liquid radiochromatography. A sample of perspiration from one subject was analyzed. The effects of physical exercise on the plasma concentration and urinary excretion of PCP were also studied. Multiple linear regression analysis showed the logarithm of renal clearance the renal clearance of PCP. PCP and its metabolites are also excreted in perspiration. Our results support clinical reports of the importance of vigorous acidification of urine and diuresis in treatment of PCP intoxication.
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PMID:Urine pH and phencyclidine excretion. 712 4

1. Dialysed giant axons from the squid have been used to study some of the properties of the Na+ fluxes when the Na+ pump is fully inhibited by strophanthidin. 2. In axons which had been depleted of ATP, strophanthidin had no effect on Na+ efflux. Similar negative results were obtained in axons dialysed with and without internal or external K+, and with or without 100 microM-internal Ca2+. 3. In the presence of 60 mM-internal Na+, 440 mM-external Na+ and strophanthidin, the fluxes of Na+ had the following characteristics. (i) ATP stimulated an efflux and an influx of Na+ of similar magnitude. The K1/2 for ATP, measured from its effect on Na+ efflux, was about 200 microM. (ii) The non-hydrolysable ATP analogue adenylyl(beta, gamma-methylene)-diphosphonate (AMP-PCP), at 2 mM concentration, either alone or in combination with 2 mM-internal phosphate, failed to stimulate any efflux of Na+. (iii) The ATP-dependent Na+ efflux was not affected by removal of internal or external K+, or external Mg2+ or Ca2+, and was not dependent on internal Ca2+. (iv) within the resolution of the method, all the ATP-dependent Na+ influx required internal Na+, and all the ATP-dependent Na+ efflux required external Na+. From the magnitude of the unidirectional Na+ fluxes the stoichiometry seemed to be a 1 to 1 Na+--Na+ exchange. 4. The ATP-internal Na+-dependent influx of Na+ in the presence of strophanthidin was not affected by 1 mM-vandate in the dialysis solution, a concentration which fully inhibits the Na+ efflux through the Na+ pump that is activated by external K+. 5. In the presence of external Na+, the external K+ sites of the Na+ pump are completely saturated with 100 mM-external K+. In unpoisoned axons incubated with 100 mM-external K+, replacement of external Na+ with Tris+ produced no change in the efflux of Na+. However, in axons poisoned with 50 microM-strophanthidin, replacement of external Na+ with Tris+ resulted in a reversible inhibition of Na+ efflux. This could suggest that strophanthidin poisoning might induce Na+ (cations?) fluxes which are not present in normal conditions.
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PMID:An ATP-dependent sodium-sodium exchange in strophanthidin poisoned dialysed squid giant axons. 731 Jul 19

The LD50 of phencyclidine (PCP, 234 mumol/kg, i.p.) in male Swiss mice decreased by 62% in animals pretreated with 2-diethylamino-2,2-diphenylvalerate hydrochloride (SKF-525A, 40 mg/kg), and increased by 74% and 20% in animals pretreated with sodium phenobarbital (75 mg/kg), and 3-methylcholanthrene (70 mg/kg), respectively, No Significant change in the LD50 was observed with cysteine or diethylmaleate pretreatment. The treatment with PCP at 179 mumol/kg/day i.p. for 7 days resulted in body weight decrement in the first 2 days and gradual increment thereafter. The increase was only 33% of the control group. The food intake was also lower in the PCP treated group of animals. PCP withdrawal led to an increase in food intake as well as body weight at a normal rate. The ratio of liver weight to body weight was not significantly higher than that of control during the treatment period. The administration of PCP for 7 days did not alter the activities of liver function enzyme markers. However, within 12 h of the initial PCP treatment a 85% increase in activity of serum glutamicoxalacetic transaminase was observed. Later the enzyme activity reached close to normal levels. No liver lesions at the light microscopic level were observed. Treatment of mice for 4 days with PCP (179 mumol/kg) caused no significant change in pentobarbital sleeping time.
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PMID:The role of hepatic microsomal enzymes in the modulation of phencyclidine-induced toxicity. 734 14

Four cDNA-encoding G-activated inwardly rectifying K+ channels have been cloned recently (Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N., and Jan, L. Y. (1993) Nature 364, 802-806; Lesage, F., Duprat, F., Fink, M., Guillemare, E., Coppola, T., Lazdunski, M., and Hugnot, J. P. (1994) FEBS Lett. 353, 37-42; Krapivinsky, G., Gordon, E. A., Wickman, K., Velimirovic, B., Krapivinsky, L., and Clapham, D. E. (1995) Nature 374, 135-141). We report the cloning of a mouse GIRK2 splice variant, noted mGIRK2A. Both channel proteins are functionally expressed in Xenopus oocytes upon injection of their cRNA, alone or in combination with the GIRK1 cRNA. Three GIRK channels, mGIRK1-3, are shown to be present in the brain. Colocalization in the same neurons of mGIRK1 and mGIRK2 supports the hypothesis that native channels are made by an heteromeric subunit assembly. GIRK3 channels have not been expressed successfully, even in the presence of the other types of subunits. However, GIRK3 chimeras with the amino- and carboxyl-terminal of GIRK2 are functionally expressed in the presence of GIRK1. The expressed mGIRK2 and mGIRK1, -2 currents are blocked by Ba2+ and Cs+ ions. They are not regulated by protein kinase A and protein kinase C. Channel activity runs down in inside-out excised patches, and ATP is required to prevent this rundown. Since the nonhydrolyzable ATP analog AMP-PCP is also active and since addition of kinases A and C as well as alkaline phosphatase does not modify the ATP effect, it is concluded that ATP hydrolysis is not required. An ATP binding process appears to be essential for maintaining a functional state of the neuronal inward rectifier K+ channel. A Na+ binding site on the cytoplasmic face of the membrane acts in synergy with the ATP binding site to stabilize channel activity.
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PMID:Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. 749 85

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.
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PMID:Hyperkalemia and high-dose trimethoprim/sulfamethoxazole. 763 23


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