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)

1. A human neuroblastoma cell line, SH-SY5Y, was used to study the effects of phencyclidine (PCP) on microtubule-associated tau protein, which acts in vivo chiefly to induce the assembly of tubulin and in vitro to promote microtubule polymerization. 2. PCP (1.0 mM) decreased tau protein (50 kD) in the cytoplasmic (supernatant) fraction as well as in the membrane (pellet) fraction. 3. These changes in tau protein were accompanied by decreases of 30-95% in cell number after concentrations of PCP, 0.25-1.0 mM, respectively. 4. After 0.5 mM PCP cytoplasmic and membrane fractions of SH-SY5Y cells showed 100 and 84% increases in total protein, respectively.
Gen Pharmacol 1992 May
PMID:Changes in microtubule-associated tau protein in human neuroblastoma cells after phencyclidine. 151 52

Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity. PK 9084 (5-40 mg/kg, ip) and CGS 9896 (2-20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15-1788 (15 mg/kg), CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH. Differently from anxiolytics, MK-801 (0.5-1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.
J Neural Transm Gen Sect 1991
PMID:Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia. 167 45

1. Anesthetized dogs were given phencyclidine HCl (PCP) by intracerebroventricular (i.c.v.) injection. 2. Physiological parameters were monitored after consecutive doses of 0.5, 1.0 and 2.0 mg of PCP. 3. Dose-related changes seen, including bradycardia, hypotension and bradypnea, were opposite to those produced by i.v. doses. 4. Single doses of 1.0 or 2.0 mg of PCP confirmed the prior observations, and the latter provided the baseline for further observations on dogs receiving PCP before various i.c.v. pretreatments--atropine, haloperidol, phentolamine or propranolol--in efforts to characterize the central neurotransmitter system(s) involved in the PCP effects.
Gen Pharmacol 1991
PMID:Respiratory and circulatory effects of centrally administered phencyclidine in anesthetized dogs. 176 Dec

1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP.
Gen Pharmacol 1991
PMID:Factors in the lethality of i.v. phencyclidine in conscious dogs. 193 8

1. Drugs with phencyclidine (PCP)-like activity in behavioural discrimination and [3H]PCP binding studies share anticonvulsant properties. 2. We have compared the rank order potency of a series of PCP-like compounds as N-methylaspartate (NMA) antagonists, determined from previously published studies from our laboratory, with their rank order anticonvulsant potencies as determined by two independent research groups in three different in vivo models of experimentally-induced epilepsy. 3. Rank order potency for NMA antagonism correlated well with rank order anticonvulsant potency. Furthermore, the systemic doses required for an effective blockade of NMA-evoked excitations were, in most cases, similar to those which produced anticonvulsant activity. 4. The results suggest that functional NMA antagonism may underlie the shared anticonvulsant properties of structurally dissimilar compounds with PCP-like activity.
Gen Pharmacol 1990
PMID:Anticonvulsant actions of phencyclidine receptor ligands: correlation with N-methylaspartate antagonism in vivo. 218 17

Ionic gradients imposed by choline Cl replacement of K methanesulfonate (Mes) at constant [K][Cl] product stimulate 45Ca efflux from skinned muscle fibers; a small, sustained Ca2+-insensitive efflux component, observed in EGTA, appears to grade a much larger Ca2+-dependent component responsible for contractile activation and is likely to reflect intermediate steps in excitation-contraction coupling. The present studies examined ATP-related effects on the Ca2+-insensitive stimulation. 45Ca efflux was measured on segments of frog semitendinosus muscle skinned by microdissection, with isometric force monitored continuously. The Ca2+-insensitive component was potentiated by quercetin, a flavonoid thought to inhibit the sarcoplasmic reticulum (SR) Ca pump by stabilizing a phosphorylated intermediate. Quercetin increased the stimulated net 45Ca release in the absence of EGTA, as expected from inhibition of reaccumulation, but its effectiveness in EGTA indicated potentiation of unidirectional efflux as such. Quercetin also increased unstimulated (control) 45Ca efflux in EGTA, to a smaller extent; potentiation appeared to be a function of efflux, with stimulation above control loss increased approximately 2.6-fold. ATP removal before stimulation, which led to rigor force and increased stiffness, prevented all quercetin effects in EGTA. ATP removal by itself inhibited ionic stimulation of the Ca2+-insensitive component, with little residual increase above the parallel control loss. Addition of the nonhydrolyzable ATP analogue AMP-PCP ([adenylyl-beta,gamma-methylene]diphosphate) (0.8 mM) after ATP removal gave similar results to ATP-free solution, which suggests that adenine nucleotide binding alone does not support stimulation by choline Cl. These results imply a fundamental role for ATP in the excitation of skinned fibers by imposed diffusion potentials; they also suggest that ATP regulates the SR Ca efflux channel, in a manner that could provide the positive feedback in Ca2+-dependent Ca release.
J Gen Physiol 1985 Dec
PMID:Excitation of skinned muscle fibers by imposed ion gradients. II. Influence of quercetin and ATP removal on the Ca2+-insensitive component of stimulated 45Ca efflux. 241 70

1. Chronic treatment of genetically hypertensive and normotensive rats with phencyclidine (PCP) resulted in changes in norepinephrine (NE) concentration in regions of the brain and in the adrenal gland. 2. Chronic PCP treatment resulted in an 18% increase in hypothalamic NE in hypertensive rats and a 20% increase in NE in the medial lower brainstem of normotensive rats. 3. Hypertensive rats also showed a 28% decrease in adrenal NE after PCP treatment.
Gen Pharmacol 1989
PMID:Changes in norepinephrine concentration following chronic administration of phencyclidine (PCP) to genetically hypertensive and normotensive rats. 260 24

1. The effects of phencyclidine (PCP) on spinal reflexes and the excitability of motoneuron somata were studied in rats. 2. PCP decreased both the monosynaptic reflex (MSR) and the polysynaptic reflex (PSR) in spinal rats as well as in intact rats. 3. The effects of PCP were not antagonized by monoaminergic and cholinergic antagonists. 4. A low dose of PCP antagonized the PSR augmentation but not the MSR augmentation caused by N-methyl-D-aspartate (NMDA). 5. In the excitability test, PCP decreased not only the monosynaptic response but also the excitability of motoneuron somata. 6. These results suggest that the inhibitory effects of PCP on spinal reflexes are not due to mediation of the monoaminergic and cholinergic systems, but partly due to its blockade of NMDA-type receptors and also to a hyperpolarizing action or a membrane-stabilizing action on the motoneuron soma.
Gen Pharmacol 1988
PMID:Inhibitory effect of phencyclidine on rat spinal reflexes. 306 95

In vivo microdialysis was used to study the effects of systemically administered phencyclidine (PCP, 10 mg/kg) on the extracellular levels of dopamine, dihydroxyphenylacetate (DOPAC), homovanillate (HVA), 5-hydroxy-indolacetate (5-HIAA), gamma-aminobutyrate (GABA), glutamate, and aspartate in the rat dorsolateral striatum. In order to demarcate the effects of anesthesia, tissue trauma and gliosis, the effect of PCP was studied in both anesthetized rats with long and short probe implantation periods and in conscious rats with a long probe implantation period. PCP significantly increased the extracellular levels of dopamine in all experimental groups, though the post-implantation interval and anesthesia modulated the degree of increase. PCP increased 5-HIAA levels in both conscious and anesthetized rats after a long post-implantation period and HVA only in anesthetized rats after a long post-implantation period. Glutamate, aspartate, and DOPAC were not affected by PCP challenge but our study indicated for the first time that systemic PCP elevates extracellular GABA in conscious rats.
J Neural Transm Gen Sect 1994
PMID:Systemic phencyclidine administration is associated with increased dopamine, GABA, and 5-HIAA levels in the dorsolateral striatum of conscious rats: an in vivo microdialysis study. 753 16

1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled pool from a hidden platform, without stereotyped behavior. 2. The sigma-selective ligand, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethyl-amine monohydrochloride), attenuates the effects of PCP in this procedure. 3. The serotonin2 (5-HT2) antagonist, ritanserin, and the sigma receptor ligands, 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine HBr (Dup734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1- (cyclopropylmethyl)piperidine (XJ448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802) and rimcazole similarly attenuate the effects of PCP. 4. The dopamine D2/sigma ligands, haloperidol and cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4- methylaminobenzamide (YM-09151-2) completely reverse the effects of PCP, whereas the same dose ranges of these drugs produce sedation. 5. The dopamine D2-selective antagonist, sulpiride, has no apparent effect on the PCP latency to the rat dive. 6. Thus, PCP-induced diving behavior was improved by sigma ligands and the 5-HT2 antagonist. This model of negative symptoms in an experimental animal will facilitate experiments on drug treatments for schizophrenia.
Gen Pharmacol 1995 Jan
PMID:The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat diving model. 771 58


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