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)

Three groups of female Sprague-Dawley rats (n = 4) were conditioned to drink water during a daily 2 hr session. The water was then changed to a solution of 1.0 mg/ml lithium chloride producing average doses between 62.9 and 72.1 mg/kg/day for Groups I and II. These rats were challenged with 4 mg/kg PCP i.p. before and during lithium treatment. Group I was tested for spontaneous locomotor activity in the open field apparatus. Lithium alone did not affect activity. After 1, 2, and 3 weeks of chronic lithium, PCP-induced activity increased 2.1, 1.7, and 2.8 fold, respectively, relative to PCP-induced activity during limited access to water only. Whole brain homogenates from Group II, after one week of chronic lithium, were used for receptor binding experiments using [3H] PCP; Group III served as water controls. The Kd (nM +/- S.E.M.) was not different in untreated (146.39 +/- 18.95) and lithium-treated (181.22 +/- 14.35) rats. The Bmax (pmole/mg protein +/- S.E.M.), however, was increased 48% (p less than 0.01) from 1.50 +/- 0.08 to 2.22 +/- 0.10 after lithium. These preliminary results suggest that chronic administration of lithium modifies the behavioral effects of PCP possibly via alterations at the receptor level.
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PMID:Behavioral and receptor binding studies of phencyclidine (PCP) and lithium interaction in the rat. 300 91

Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar and schizoaffective disorders and has recently been shown to have neuroprotective properties. The present study used organotypic corticostriatal slices taken from postnatal day 2 rat pups to investigate the protective effect of lithium and the role of the phosphatidylinositol-3 kinase (PI-3K)/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways in PCP-induced cell death. Lithium pretreatment dose-dependently reduced PCP-induced caspase-3 activation and DNA fragmentation in layers II to IV of the cortex. PCP elicited time-dependent inhibition of the MEK/ERK and PI-3K/Akt pathways, as indicated by dephosphorylation of ERK1/2 and Akt. The proapoptotic factor glycogen synthase kinase (GSK)-3beta was also dephosphorylated at serine 9 and thus activated. Lithium prevented PCP-induced inhibition of the two pathways and activation of GSK-3beta. Furthermore, blocking either PI-3K/Akt or MEK/ERK pathway abolished the protective effect of lithium, whereas inhibiting GSK-3beta activity mimicked the protective effect of lithium. However, no cross-talk between the two pathways was found. Finally, specific GSK-3beta inhibition did not prevent PCP-induced dephosphorylation of Akt and ERK. These data strongly suggest that the protective effect of lithium against PCP-induced neuroapoptosis is mediated through independent stimulation of the PI-3K/Akt and ERK pathways and suppression of GSK-3beta activity.
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PMID:Lithium protection of phencyclidine-induced neurotoxicity in developing brain: the role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. 1854 76