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)

Although reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1 receptor activation, the implications of A2 receptor activation on synaptic transmission have not been well explored. We examined the role adenosine A2 receptors play in the efficacy of neurotransmission between the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice. A2 receptor blockade in the presence of complete A1 receptor inhibition led to a reversible reduction of the field excitatory post-synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033 Hz) indicating that A2 receptors can enhance synaptic transmission. A2 receptor blockade by the A2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In contrast, no such effect on LTP induction was observed during A1 receptor blockade. We also examined the effects of DMPX on the induction of LTP during continued A1 receptor blockade with CPT. Under this condition, LTP was significantly reduced when compared to LTP induced in the presence of CPT alone. A similar result was found using the highly polar A2 antagonist 8-SPT (8-(p-sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due to a direct action on an intracellular intermediate. DMPX had no effect on LTP expression if applied 45 min following the tetanus indicating that A2 receptors play no significant role in the maintenance phase of LTP. Selective A2a receptor activation did not alter the field EPSP. Similarly, selective blockade of the A2a receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing rates can result in elevations in the concentration of extracellular adenosine. Together, these results suggest that the A2 receptors may play an important role in the induction although not the maintenance of hippocampal LTP and that the effect is likely to be mediated by the A2b receptor.
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PMID:A role for adenosine A2 receptors in the induction of long-term potentiation in the CA1 region of rat hippocampus. 918 31

The effects of an adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (8-CPT, 1 microM), on the reduction of long-term potentiation were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of long-term potentiation (depotentiation) was achieved by delivering a train of low-frequency afferent stimuli (low-frequency stimulation, 1000 pulses, 1 Hz) 20 min after the tetanus (100 Hz, 100 pulses). In control experiments, low-frequency stimulation reduced the potentiated component of the slope of the field EPSP and the amplitude of the population spike by 68.5 +/- 14.4% and 80.1 +/- 8.8%, respectively (n = 6); these values were significantly reduced to 13.4 +/- 9.7% and 9.0 +/- 10.9% (n = 7) when the low-frequency stimulation was applied during the perfusion with 8-CPT (1 microM). These results indicate that activation of adenosine A1 receptors enhances the depotentiation of long-term potentiation.
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PMID:8-cyclopentyltheophylline, an adenosine A1 receptor antagonist, inhibits the reversal of long-term potentiation in hippocampal CA1 neurons. 927 23

A train of low-frequency afferent stimuli (LFS, 1 Hz, 1000 pulses), given 60 min prior to a tetanus (100 Hz, 100 pulses), suppresses the induction of long-term potentiation (LTP) in which a short-term potentiation decreases gradually back to the pre-tetanic level within 40-50 min (LTP suppression). We investigated the effects of adenosine A1 or A2 receptor antagonists (8-cyclopentyltheophylline (8-CPT) and CP-66713, respectively) on LTP suppression in CA1 neurons of guinea pig hippocampal slices. When the LFS was delivered in the presence of 8-CPT (1 microM), LTP suppression was not significantly affected. However, when LFS was delivered in the presence of CP-66713 (10 microM), LTP suppression was inhibited, leading to successful LTP induction. These results indicate that endogenous adenosine, acting via A2 receptors, is involved in the mechanism of LTP suppression.
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PMID:Endogenous adenosine regulates the effects of low-frequency stimulation on the induction of long-term potentiation in CA1 neurons of guinea pig hippocampal slices. 1067 36

cAMP is a critical second messenger involved in synaptic transmission and synaptic plasticity. Here, we show that activation of the adenylyl cyclase by forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and occluded tetanus-induced long-term potentiation (LTP) in subicular bursting neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89. Variations in the degree of EPSC blockade by the low-affinity competitive AMPA receptor-antagonist gamma-d-glutamyl-glycine (gamma-DGG), analysis of the coefficient of variance as well as changes in short-term potentiation suggest an increase of glutamate concentration in the synaptic cleft after expression of LTP. We conclude that presynaptic LTP in bursting cells requires activation of PKA by a calcium-dependent adenylyl cyclase while LTP in regular firing cells is independent of elevated cAMP levels. Our results provide evidence for a differential role of cAMP in LTP at hippocampal output synapses.
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PMID:Differential cAMP signaling at hippocampal output synapses. 1911 68