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)

When the histamine (HA) turnover in the brain of mice was estimated on the basis of the pargyline-induced accumulation of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, the enhancing effect of phencyclidine (PCP) on the HA turnover was antagonized by a large dose of naloxone. However, a dopamine receptor antagonist haloperidol, which is also a potent sigma receptor antagonist, did not inhibit the effect of PCP on the HA turnover. [D-Ala2,D-Leu5]enkephalin, a prototypic delta opioid agonist, markedly enhanced the HA turnover. The effect of this peptide was demonstrated not only when the HA turnover was determined by the pargyline-induced t-MH accumulation but when it was estimated by the HA depletion induced by alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. A sigma agonist, SKF-10047, and a kappa agonist, ethylketazocine, had no PCP-like enhancing effect on the HA turnover. These results suggest that PCP enhances the brain HA turnover in mice by stimulating, probably indirectly, endogenous opioid systems.
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PMID:Involvement of opioid receptors in phencyclidine-induced enhancement of brain histamine turnover in mice. 288 77

We compared the effects of phencyclidine (PCP) and methamphetamine on body temperature and brain histamine turnover in mice. Methamphetamine at 5 and 10 mg/kg produced dose-related increases in rectal temperature, whereas PCP given in the same doses had no significant effect. In mice pretreated with alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, PCP produced a marked hyperthermia. PCP markedly accelerated brain histamine turnover, as measured by the accumulation of tele-methylhistamine, a predominant metabolite of brain histamine, following administration of pargyline. Methamphetamine had no significant effect on the histamine dynamics. These results suggest involvement of brain histaminergic neurons in the action of PCP but not methamphetamine, and the presence of a histaminergic thermoregulatory mechanism.
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PMID:Comparison of effects of phencyclidine and methamphetamine on body temperature in mice: a possible role for histamine neurons in thermoregulation. 371 74

The effects of phencyclidine (PCP) on the dynamics of brain histamine (HA) were examined in the mouse brain. PCP (2-10 mg/kg i.p.) dose-dependently elevated the level of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, without altering the HA level. PCP also enhanced the accumulation of t-MH after administration of pargyline hydrochloride (80 mg/kg i.p.). PCP at 5 mg/kg facilitated the HA depletion produced by (S)-alpha-fluoromethylhistidine markedly (50 mg/kg i.v.), a specific inhibitor of histidine decarboxylase. Metoprine (10 mg/kg i.p.), an inhibitor of HA-N-methyltransferase, decreased the t-MH level and increased the HA level. In the metoprine-treated mice, PCP at 10 mg/kg had no significant effect on the t-MH level, whereas it significantly increased the HA level. The increase in the t-MH level after administration of PCP (5 mg/kg) was observed in various brain regions except the pons-medulla oblongata. These results suggest that, in mice, PCP increases the brain HA turn-over possibly by facilitating the release of HA.
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PMID:Phencyclidine and the dynamics of mouse brain histamine. 407 33

The modulation of histamine neuron activity by various non-competitive NMDA-receptor antagonists was evaluated by changes in tele-methylhistamine (t-MeHA) levels and histidine decarboxylase (hdc) mRNA expression induced in rodent brain. The NMDA open-channel blockers phencyclidine (PCP) and MK-801 enhanced t-MeHA levels in mouse brain by 50-60%. Ifenprodil, which interacts with polyamine sites of NR2B-containing NMDA receptors, had no effect. PCP also increased hdc mRNA expression in the rat tuberomammillary nucleus. The enhancement of t-MeHA levels elicited by MK-801 (ED50 of approximately 0.1 mg/kg) was observed in the hypothalamus, cerebral cortex, striatum and hippocampus. Control t-MeHA levels and the t-MeHA response to MK-801 were not different in male and female mice. Double immunostaining for HDC and NMDA receptor subunits showed that histamine neurons of the rat tuberomammillary nucleus express NMDA receptor subunit 1 (NR1) with NMDA receptor subunit 2A (NR2A) and NMDA receptor 2B subunit (NR2B). In addition, immunoreactivity for the neuronal glutamate transporter EAAC1 was observed near most histaminergic perikarya. Hence, these findings support the existence of histamine/glutamate functional interactions in the brain. The increase in histamine neuron activity induced by NMDA receptor antagonists further suggests a role of histamine neurons in psychotic disorders. In addition, the decrease in MK-801-induced hyperlocomotion observed in mice after administration of ciproxifan further strengthens the potential interest of H3-receptor antagonist/inverse agonists for the symptomatic treatment of schizophrenia.
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PMID:N-methyl-D-aspartate receptor antagonists enhance histamine neuron activity in rodent brain. 1692 61