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 effects of acute and chronic phencyclidine (PCP) administration on neurotensin-like immunoreactivity (NTLI) were investigated in discrete regions of rat brain. Both acute and chronic administration of PCP induced high locomotor activity, stereotypy and ataxia. On PCP administration, NTLI decreased significantly in the frontal cortex (Fc) alone. These results suggest that the decrease in NTLI in Fc is related to the behavioral abnormalities produced by PCP.
 ...
PMID:Effects of phencyclidine administration on behavior and brain neurotensin-like immunoreactivity in rats. 403 20

Porcine brain contained an active factor that competed with [3H]-phencyclidine (PCP) for binding to rat brain membranes. On reverse phase high pressure liquid chromatography, the active material eluted between 38-42% acetonitrile. Gel filtration chromatography of the factor predicted a molecular weight of approximately 3000 daltons. The endogenous substance appeared to be selective for PCP receptors as it did not interact with either benzodiazepine, neurotensin, nor with mu, delta, or kappa opioid receptors. The active material showed a heterogenous distribution in brain, with highest concentrations found in hippocampus and cortex. It is likely to be a small peptide since various proteases eliminated or markedly reduced the potency of the compound in a [3H]-PCP binding assay. The material also possessed PCP-like activity in two bioassays. Like PCP, it induced contralateral rotational behavior after unilateral intranigral injection and depressed spontaneous cell activity after iontophoretic micropressure application in hippocampus and cerebral cortex. Thus, this small peptide is likely to be an endogenous ligand for the PCP receptor.
 ...
PMID:Evidence for an endogenous peptide ligand for the phencyclidine receptor. 609 23

Although phencyclidine (PCP) has several neurochemical effects, the most pharmacologically relevant are thought to be its ability to antagonize the activity of N-methyl-D-aspartate (NMDA)-type glutamate receptors and to increase extracellular dopamine concentrations. In order to elucidate the nature and consequence of PCP actions on glutamatergic and dopaminergic pathways, this study examined the response of extrapyramidal and limbic neurotensin systems to this drug. Multiple, but not single, doses of PCP caused increases in striatal neurotensin-like immunoreactivity content of 150-200% of control. These effects were blocked by the dopamine D1 receptor antagonist, SCH 23390, suggesting they were caused by PCP-mediated enhanced dopamine activity at dopamine D1 receptors. In contrast, MK-801 (dizocilpine), a selective NMDA receptor antagonist that acts at the same site as PCP, had no effect on neurotensin-like immunoreactivity content when given alone. In addition, coadministration of MK-801 with PCP did not alter the effect of PCP on striatal neurotensin-like immunoreactivity content. This lack of effect suggests that the actions of PCP on NMDA receptors was not involved in the neurotensin response. The PCP effect on neurotensin striatal pathways also appeared not to be associated with the dopamine D2 or gamma-aminobutyric acid (GABA) systems: a possible role for the sigma receptor in this effect could not be eliminated. Administration of multiple doses of PCP also affected neurotensin-like immunoreactivity content in the nucleus accumbens (160% compared to control) and frontal cortex (40% compared to control), but not the substantia nigra. The neurotensin effects of PCP are compared to those of another psychotomimetic drug of abuse, methamphetamine.
 ...
PMID:Response of extrapyramidal and limbic neurotensin systems to phencyclidine treatment. 767 1

The longitudinal distribution of brush-border endopeptidase-24.11, endopeptidase-2, aminopeptidase W, angiotensin-converting enzyme (ACE), dipeptidyl peptidase IV (DPP IV), carboxypeptidase P, and aminopeptidase P in the rat intestine was determined. The jejunum has the highest activities of endopeptidase-24.11 and ACE while the ileum has the highest activities of aminopeptidase W and carboxypeptidase P, and the jejunoileal junction has the highest activity of aminopeptidase P. The jejunum and ileum have similar activities of DPP IV. The profiles of differential hydrolysis of neurotensin and acetylneurotensin (8-13) along the intestine agree with distribution of endopeptidase-24.11 and ACE, suggesting that amino acid sequences of peptides and the substrate specificity of enzymes will determine site-dependent hydrolysis. There is substantial similarity in the intestinal distribution of peptidases in the human, rat, and rabbit.
 ...
PMID:Distribution of brush-border membrane peptidases along the rat intestine. 793 32

The effects of systemically administered phencyclidine (PCP; 2.5 mg/kg, s.c.) and D-amphetamine (1.5 mg/kg, s.c.) on the extracellular concentrations of neurotensin-like immunoreactivity (NT-LI) and dopamine (DA) in the ventral striatum (vSTR) and the medial prefrontal cortex (mPFC) were studied in freely moving rats using microdialysis. In separate animals, the effects of PCP and D-amphetamine on open field activity were also analyzed. PCP, but not D-amphetamine, caused a significant increase (156% over baseline) of NT-LI levels in the vSTR which was relatively short lasting, i.e., of less than 2 h duration. In contrast, both drugs significantly increased NT-LI concentrations in the mPFC by almost 100% during the same period. PCP and D-amphetamine also significantly increased extracellular levels of DA in the vSTR by 83 and 364%, respectively. However, the peak effect of PCP on DA appeared later than that of D-amphetamine, i.e., at 150 and 60 min, respectively, after drug administration. Also in the mPFC, both PCP and D-amphetamine significantly increased DA concentrations by 98 and 284%, respectively. Generally, effects on DA levels of both PCP and D-amphetamine were, in contrast to their effects on NT-LI levels, clearly more long-lasting, i.e., of 3-4 h duration. Behaviorally, D-amphetamine produced a more pronounced, general activation than PCP, with a faster onset of activation, i.e. within 30 vs 90 min after administration. However, both drugs produced long-lasting effects on the spatial organization of behavioral activity, which lasted for 3-4 h. In conclusion, the more pronounced behavioral stimulation by D-amphetamine (1.5 mg/kg, s.c.) vs PCP (2.5 mg/kg, s.c.) in the rat may largely be explained by its more potent DA-releasing effect in the brain. Initial behavioral suppression by PCP, e.g., of rearing, as well as its rather poor locomotor stimulant action in general, might relate to release of NT in the vSTR. The long-lasting, behavioral disorganization by both PCP and D-amphetamine may, however, be related to increased release of DA rather than NT in the mesolimbocortical areas.
 ...
PMID:Effects of D-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat. 878 63

Neurotensin is an endogenous neuropeptide closely associated with the mesolimbic dopaminergic system and shown to possess antipsychotic-like effects. In particular, acute neurotensin receptor activation can inhibit conditioned avoidance response (CAR), attenuate phencyclidine (PCP)-induced prepulse inhibition (PPI) disruptions, and reverse PCP-induced hyperlocomotion. However, few studies have examined the long term effects of repeated neurotensin receptor activation and results are inconsistent. Since clinical administration of antipsychotic therapy often requires a prolonged treatment schedule, here we assessed the effects of repeated activation of neurotensin receptors using an NTS1 receptor selective agonist, PD149163, in 3 behavioral tests of antipsychotic activity. We also investigated whether reactivity to the atypical antipsychotic clozapine was altered following prior PD149163 treatment. Using both normal and prenatally immune activated rats generated through maternal immune activation with polyinosinic:polycytidylic acid, we tested PD149163 in CAR, PCP (1.5mg/kg)-induced PPI disruption, and PCP (3.2mg/kg)-induced hyperlocomotion. For each paradigm, rats were first repeatedly tested with vehicle or PD149163 (1.0, 4.0, 8.0mg/kg, sc) along with vehicle or PCP for PPI and hyperlocomotion tests, then challenged with PD149163 after 2 drug-free days. All rats were then challenged with clozapine (5.0mg/kg, sc). During the repeated test period, PD149163 exhibited antipsychotic-like effects in all three models. On the PD149163 challenge day, prior drug treatment only caused a tolerance effect in CAR. This tolerance in CAR was transferrable to clozapine, as it enhanced clozapine tolerance in the same group of animals. Although no tolerance effect was seen in the PD149163 challenge for the PCP-induced hyperlocomotion test, the clozapine challenge showed increased sensitivity in groups previously exposed to repeated PD149163 treatment. Our findings suggest that repeated exposure to NTS1 receptor agonists can induce a dose-dependent tolerance and cross-tolerance to clozapine to some of its behavioral effects but not others.
...
PMID:Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: assessing for tolerance and cross-tolerance to clozapine. 2543 25