Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is thought to act as an endogenous anticonvulsant and neuroprotective substance in the brain. In the present study we compared neuronal death following status epilepticus (SE) induced in the presence of 8-cyclopentyl-1,3-dimethylxanthine (8-CPT), an A1-adenosine receptor antagonist, with that following SE induced by continuous hippocampal stimulation. Hippocampal damage was characterized using selective nerve and nonnerve cell markers. Six days after SE, both models produced similar patterns of CA1 and CA3 cell loss and selective loss of parvalbumin and hilar somatostatin-immunoreactive interneurons. Calbindin D28K-immunoreactive interneuron numbers and calbindin D28K immunoreactivity in dentate granule cells remained unchanged although calbindin D28K staining was lost in damaged CA1 neurons. Neuronal injury in these areas was also accompanied by reactive gliosis and microglial proliferation, as well as the production of basic fibroblast growth factor and insulin-like growth factor-1 by astrocytes. Although hippocampal damage appeared to be more severe after SE induced in the presence of 8-CPT, this may be due to the increased severity of SE generated in this model.
 ...
PMID:Neuronal injury following electrically induced status epilepticus with and without adenosine receptor antagonism. 764 19

The mechanisms underlying the depression of evoked fast excitatory postsynaptic currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in vitro ischemia) for a 4-min period in hippocampal CA1 neurons were investigated in rat brain slices. The amplitude of evoked fast EPSCs decreased by 85 +/- 7% of the control 4 min after the onset of in vitro ischemia. In contrast, the exogenous glutamate-induced inward currents were augmented, while the spontaneous miniature EPSCs obtained in the presence of tetrodotoxin (TTX, 1 microM) did not change in amplitude during in vitro ischemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pulse stimulation (40-ms interval), and the amplitude of the second fast EPSC increased to 156 +/- 24% of the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio) increased during in vitro ischemia. Pretreatment of the slices with adenosine 1 (A1) receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the depression of the fast EPSCs, in a concentration-dependent manner: in the presence of 8-CPT (1-10 microM), the amplitude of the fast EPSCs decreased by only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic volleys and excitatory postsynaptic field potentials (fEPSPs) were extracellularly recorded in a proximal part of the stratum radiatum in the CA1 region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On the other hand, the amplitudes of the first and second presynaptic volley, which were abolished by TTX (0.5 microM), did not change during in vitro ischemia. The maximal slope of the Ca(2+)-dependent action potential of the CA3 neurons, which were evoked in the presence of 8-CPT (1 microM), nifedipine (20 microM), TTX (0.5 microM), and tetraethyl ammonium chloride (20 mM), decreased by 12 +/- 6% of the control 4 min after the onset of in vitro ischemia. These results suggest that in vitro ischemia depresses the evoked fast EPSCs mainly via the presynaptic A1 receptors, and the remaining 8-CPT-resistant depression of the fast EPSCs is probably due to a direct inhibition of the Ca(2+) influx to the axon terminals.
 ...
PMID:Mechanisms underlying the depression of evoked fast EPSCs following in vitro ischemia in rat hippocampal CA1 neurons. 1153 60

We tested a proposal that the hyperpolarization-activated cation channel (I(h) channel) is involved in the induction of short- and long-term plasticity at the hippocampal mossy fiber-CA3 synapses. Bath application of a specific I(h) channel blocker ZD 7288, at a concentration at which it blocked I(h) channels, substantially depressed mossy fiber synaptic transmission, and this inhibition was occluded by previous blockade of these channels by CsCl. In addition, ZD 7288 attenuated the amplitude of both AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) equally and caused a coincident increase in the failure rate of single-fiber EPSCs and paired-pulse facilitation (PPF). It also blocked long-term potentiation (LTP) induction when applied before high-frequency tetanic stimulation (TS), and reversed LTP when applied afterwards. Continuous application of CsCl, which efficiently blocks I(h) channels, mimicked ZD 7288 in inhibiting LTP. Furthermore, ZD 7288 blocked both forskolin- and Sp-8-CPT-cAMPS-mediated enhancements of synaptic transmission. However, it did not affect the frequency facilitation induced by increasing the stimulus frequency from 0.05-1 Hz and the expression of the long-term depression (LTD) induced by low-frequency stimulation (LFS) or DCG-IV. Perforated patch-clamp recordings from granule cells revealed that the voltage for half-maximal activation (V(1/2)) of I(h) was significantly shifted towards the depolarizing direction following forskolin or Sp-8-CPT-cAMPS treatment. This enhanced I(h) current was not due to persistent activation of protein kinase A (PKA), because PKA inhibitor KT5720 did not abolish the difference between the activation curves. Therefore, we conclude that I(h) channels may contribute to the development and regulation of short- and long-term plasticity at the mossy fiber-CA3 synapses.
 ...
PMID:Reexamination of the role of hyperpolarization-activated cation channels in short- and long-term plasticity at hippocampal mossy fiber synapses. 1272 28