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)

The intestinal metabolism and absorption of enterostatin was studied using brush-border membrane vesicles and an in vitro model of intestinal segments from rabbit ileum mounted in Sweetana-Grass diffusion chamber. Hydrolysis of enterostatin was observed with both epithelial sheets and brush-border membranes. The main metabolite was found to be des-arginine-enterostatin. Dipeptidylpeptidase IV was found to play a minor role in enterostatin degradation, whereas carboxypeptidase P activity accounted for the initial step of peptide hydrolysis. More than 50% of the amount of enterostatin added to the mucosal compartment of the Sweetana-Grass diffusion chamber was degraded after 30 min. Enterostatin was mainly absorbed as degradation products but a small transepithelial passage of des-arginine-enterostatin and immunoreactive enterostatin was also detected. Although immunoreactive enterostatin exhibits a low apparent permeability coefficient in rabbit ileum, the luminal production of this peptide may be of physiological importance in the control of appetite.
Regul Pept 1994 Dec 15
PMID:The in vitro intestinal absorption of enterostatin is limited by brush-border membrane peptidases. 771 82

Yeast mitochondria were found to contain a novel topoisomerase-like activity which required nucleoside di- or tri-phosphates as a cofactor. ADP supported activity as effectively as ATP and the optimal concentration for each was approximately 20 microM. None of the other standard ribo- or deoxyrib-onucleotides could fully substitute for either ADP or ATP. The non-hydrolyzable ATP analogs, adenosine-5'-0-(3-thiotriphosphate) (ATP-gamma-S), adenylyl (beta,gamma-methylene) (AMP-PCP), and andenyl-imidodiphosphate (AMP-PNP) also supported activity suggesting that the nucleotide cofactor regulated topoisomerase activity rather than serving as an energy donor in the reaction. The mitochondrial topoisomerase activity relaxed both positively and negatively supercoiled DNA. It was not inhibited by concentrations of ethidium bromide up to 2 micrograms/ml nor by either nalidixic or oxolinic acids; novobiocin, coumermycin, and berenil inhibited the activity. Genetic and biochemical analysis of the mitochondrial topoisomerase activity indicated that it was not encoded by the nuclear TOP1, TOP2, and TOP3 genes.
Curr Genet 1994 Dec
PMID:Evidence for a nucleotide-dependent topoisomerase activity from yeast mitochondria. 775 Jan 44

The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-D-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (< 100 microM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (> 100 microM) resulted in profound reductions in both dopamine release in the accumbens and firing in the VTA. A strong correlation between the ability of NMDA to influence dopamine release in the accumbens and the firing rate in the VTA was observed. Perfusion with the non-competitive NMDA receptor antagonist PCP eliminated the NMDA-induced increases in extracellular dopamine in the accumbens. These data suggest that dopamine release in the accumbens and the firing rate of dopamine neurons can be both increased or decreased depending upon the magnitude of glutamatergic stimulation within the VTA.
Brain Res 1994 Dec 15
PMID:N-methyl-D-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies. 788 36

The reduction in magnitude of the startle reflex in response to a loud noise produced by prior presentation of a stimulus of lower intensity is known as prepulse inhibition (PPI). PPI may be disrupted by a variety of drugs, most notably by dopaminergic agonists such as apomorphine and by phencyclidine (PCP), and related noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Apomorphine-induced disruption of PPI is antagonized by both typical and atypical neuroleptics. The present study examined the effects of the atypical neuroleptic, clozapine, alone and in combination with PCP, on PPI in rats. The results of previous studies suggest that disruption of PPI by PCP and similar drugs is not sensitive to antagonism by typical neuroleptics such as haloperidol. The results of the present study show that clozapine's effect on PCP-induced disruption of PPI is also limited. The failure of clinically effective antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in this procedure may represent a model of attentional deficits observed in treatment-resistant schizophrenia.
Pharmacol Biochem Behav 1994 Dec
PMID:Clozapine's effects on phencyclidine-induced disruption of prepulse inhibition of the acoustic startle response. 788 71

We investigated the effect of the sigma selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK-801. Learning capacities were evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that sigma sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at sigma sites, reverses the amnesia induced by a drug acting at the PCP site.
Pharmacol Biochem Behav 1994 Dec
PMID:PRE-084, a sigma selective PCP derivative, attenuates MK-801-induced impairment of learning in mice. 788 99

Diagnostic concordance of DSM-III, DSM-IV and ICD-10 was tested in a heterogeneous unrestricted sample of 370 clinical cases drawn from a regional consortium. Agreement for abuse/harmful use, dependence, and the collapsed category of 'any diagnosis' was studied across eight drug classes. A probabilistic approach to the cross-classifications based on configural frequency analysis was applied, permitting the computation of four indices of agreement. In contrast to earlier studies, ICD-10 appeared to be the most inclusive system, and often diagnosed cases that were undiagnosed by both DSMs. Generally satisfactory coherence between the ICD-10 harmful use category and the DSM category of abuse was found, but this agreement was often due to a preponderance of negative or undiagnosed cases; disagreement was common on which cases in particular warrant a mild diagnosis. In general, the greatest diagnostic concordance was observed for sedative/hypnotics, opiates and alcohol, the poorest for amphetamines, cocaine and PCP. The analytic approach produced an array of cross-system relationships that are more complex and conditional than those previously reported, and scientists and clinicians are cautioned to study particular drugs, diagnostic levels and measures of concordance before applying cross-system results to their own data or design needs.
Drug Alcohol Depend 1994 Dec
PMID:Diagnostic concordance of substance use disorders in DSM-III, DSM-IV and ICD-10. 788 10

SDZ EAA 494 (D-CPPene) was characterized as a competitive NMDA antagonist, having a pA2 value against NMDA depolarizations in frog spinal cord and rat neocortex of 6.7-6.8 and a pKi of 7.5 in a [3H]CGP39653 binding assay, with no action on other receptors or amine reuptake. The compound was orally active in rodent maximal electroshock models with an ED50 of around 16 mg/kg, was protective in rats even 24 hours after oral application and had an oral therapeutic index of around 8. Muscle relaxation, ataxia, flattened body posture and reduced acquisition of a passive avoidance task, suggesting potential effects on memory formation, occurred at supra-anticonvulsant doses in rodents, with PCP-like stimulatory effects produced only by high i.p. doses or constant i.v. infusions. This favourable profile is discussed in relation to the negative outcome of a recent trial of the compound in patients with intractable epilepsy. The conclusion is drawn that standard models for screening new anticonvulsants are inappropriate to seeking drugs active in patients with a protracted convulsive history. The anti-ischaemic action of SDZ EAA 494 encourages further testing in brain trauma, in which the anticonvulsant action of the compound may be an added benefit.
Neurochem Int 1994 Dec
PMID:The pharmacology of SDZ EAA 494, a competitive NMDA antagonist. 789 35

The effect of a keto-derivative of cholesterol, namely, 6-ketocholestanol (5 alpha-cholestan-3 beta-ol-6-one; kCh) on the uncoupling of oxidation and phosphorylation by various uncouplers was studied in rat heart mitochondria. kCh was found to completely abolish the uncoupling effect (the increase in the respiration rate under the respiratory control conditions and the decrease in the membrane potential) caused of FCCP, CCCP and SF6847 and partially by TTFB at low concentrations of uncouplers. It was without effect on the uncoupling by PCP, DNP and palmitate. Carboxyatractylate, a specific inhibitor of the ADP/ATP-antiporter, was shown to almost completely abolish the uncoupling induced by palmitate and partially by low concentration of TTFB, PCP and DNP. Effects of high concentrations of all these uncouplers as well as of any concentrations of gramicidin proved to be kCh- and carboxyatractilate-insensitive. The data are discussed in terms of the hypothesis on the protein-mediated mechanism of the protonophorous uncoupling.
FEBS Lett 1994 Dec 05
PMID:6-ketocholestanol abolishes the effect of the most potent uncouplers of oxidative phosphorylation in mitochondria. 798 94

The 1-aminoadamantanes memantine (1-amino-3,5-dimethyl-adamantane) and amantadine (1-amino-adamantane) are clinically used as anti-parkinsonian, anti-spasticity, anti-dementia and antiviral drugs. In the present investigation we have tested a series of 1-aminoadamantane derivatives including memantine and amantadine for their ability to compete with [3H](+)-pentazocine in homogenates of post-mortem human frontal cortex. The Ki values ranged from 0.237 +/- 0.019 microM for 1-N-dimethyl-amino-3,5-dimethyl-adamantane to 20.25 +/- 16.48 microM for amantadine. The Ki value of memantine was 19.98 +/- 3.08 microM and was thus very similar to that of amantadine. Memantine, at therapeutic concentrations, probably does not interact with the sigma binding site. Amantadine, at therapeutic concentrations, probably binds both to the sigma site and to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor.
Neurosci Lett 1993 Dec 12
PMID:Affinity of 1-aminoadamantanes for the sigma binding site in post-mortem human frontal cortex. 830 17

The effects of phencyclidine (PCP; a noncompetitive NMDA antagonist) were assessed in rhesus monkeys using performance in an operant test battery (OTB) consisting of five food-reinforced tasks thought to engender responses dependent upon aspects of time estimation, short-term memory, motivation, learning, and color and position discrimination. End-points included percent task completed (PTC), response rate or latency, and response accuracy. Testing occurred 15 min after IV injections of PCP (0.00, 0.003, 0.01, 0.03, 0.1, 0.13, 0.18, and 0.3 mg/kg). PCP disrupted performance of all tasks at 0.30 mg/kg. PTC was significantly decreased in the time estimation, motivation, and learning tasks at doses > or = 0.13 mg/kg. PTC for the short-term memory and color and position discrimination tasks was significantly decreased at 0.18 mg/kg and above. Response rate was significantly decreased at 0.13 mg/kg and above in the motivation and learning tasks and at 0.18 mg/kg and above in the time estimation, short-term memory, and color and position discrimination tasks. Response accuracy was significantly decreased in the time estimation, short-term memory, and learning tasks at doses > or = 0.13 mg/kg, while accuracy in the color and position discrimination task was decreased only at 0.30 mg/kg. PCP's effects on OTB performance were generally nonspecific, in that the time estimation, short-term memory, learning, and motivation tasks were all equally sensitive, with the color and position discrimination task being the least sensitive. These results are different than those obtained from earlier studies on the effects of MK-801, a more selective noncompetitive NMDA antagonist.
Pharmacol Biochem Behav 1995 Dec
PMID:Acute behavioral effects of phencyclidine on rhesus monkey performance in an operant test battery. 858 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>