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)

This study determined the role of caspase-3 in phencyclidine (PCP)-induced neurodegeneration in postnatal rats. PCP administration to postnatal day 7 rats induced a dose-dependent increase in caspase-3 enzymatic activity in frontal cortex, striatum, and hippocampus. Enzymatic activation was present at 4 h, peaked between 6 and 12 h, and disappeared by 24 h. Further, cleaved caspase-3-immunoreactive neurons were detected as early as 2 h in the cortex, and were found throughout the brain, including, in addition, the thalamus and striatum. Within the cingulate, frontal, parietal, and retrosplenial cortices, immunoreactivity was specific for layers II-IV (especially layer II). Neurons positive for both silver staining and terminal deoxynucleotidyl transferase biotin-d-UTP nick-end labeling (TUNEL) were found in the same brain regions and subregions. Double labeling experiments confirmed that cleaved caspase-3 and TUNEL were coexpressed in many neurons in all brain regions and subregions studied. Temporal studies revealed that procaspase-3 cleavage preceded TUNEL staining by about 3 h, with many neurons being positive for both caspase-3 and TUNEL 9 h after PCP treatment. In organotypic corticostriatal slices, PCP caused a concentration- and time-dependent cleavage of procaspase-3 that was also colocalized with TUNEL staining in layers II-IV of the parietal cortex. Caspase-3 activation again preceded PCP-induced DNA damage assessed by TUNEL. PCP-induced neuronal death in vitro as measured by TUNEL staining was blocked 85% by Ac-AAVALLPAVLLALLAPDEVD-CHO, a cell-permeable selective caspase-3 inhibitor. These data demonstrate that caspase-3 activation plays a necessary role in the regionally selective neuronal death induced by PCP in the developing rat brain.
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PMID:The role of caspase-3 activation in phencyclidine-induced neuronal death in postnatal rats. 1698 4

The carotid body's physiological role is to sense arterial oxygen, CO(2) and pH. It is however, also powerfully excited by inhibitors of oxidative phosphorylation. This latter observation is the cornerstone of the mitochondrial hypothesis which proposes that oxygen is sensed through changes in energy metabolism. All of these stimuli act in a similar manner, i.e. by inhibiting a background TASK-like potassium channel (K(B)) they induce membrane depolarization and thus neurosecretion. In this study we have evaluated the role of ATP in modulating K(B) channels. We find that K(B) channels are strongly activated by MgATP (but not ATP(4)(-)) within the physiological range (K(1/2) = 2.3 mm). This effect was mimicked by other Mg-nucleotides including GTP, UTP, AMP-PCP and ATP-gamma-S, but not by PP(i) or AMP, suggesting that channel activity is regulated by a Mg-nucleotide sensor. Channel activation by MgATP was not antagonized by either 1 mm AMP or 500 microm ADP. Thus MgATP is probably the principal nucleotide regulating channel activity in the intact cell. We therefore investigated the effects of metabolic inhibition upon both [Mg(2+)](i), as an index of MgATP depletion, and channel activity in cell-attached patches. The extent of increase in [Mg(2+)](i) (and thus MgATP depletion) in response to inhibition of oxidative phosphorylation were consistent with a decline in [MgATP](i) playing a prominent role in mediating inhibition of K(B) channel activity, and the response of arterial chemoreceptors to metabolic compromise.
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PMID:Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides. 1761 4


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