Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic AMP and cyclic GMP serve as second messengers in a variety of neural cells, modulating their metabolic and electrical activity. The cyclic GMP-stimulated cyclic nucleotide phosphodiesterase, an enzyme whose hydrolytic activity is allosterically regulated by cyclic GMP in peripheral tissues, could play an important role in the regulation of cyclic nucleotide levels in the brain. To study the presence and distribution of cyclic GMP-stimulated phosphodiesterase in the rat brain, we cloned a portion of rat liver cyclic GMP-stimulated phosphodiesterase complementary DNA by polymerase chain reaction, using degenerate phosphodiesterase-specific oligonucleotide primers. Northern blot analysis of rat tissues reveals abundant expression of cyclic GMP-stimulated phosphodiesterase messenger RNA in the brain. Northern blot analysis of brain subregions shows especially strong expression in hippocampus and cortex, modest expression in the remainder of the forebrain and in the midbrain, and little expression in cerebellum and hindbrain. In situ hybridization studies with cyclic GMP-stimulated phosphodiesterase riboprobes confirm these northern blot results, and delineate cell groups with high levels of expression. Medial habenular nucleus is intensely labeled, as is hippocampus in the vicinity of pyramidal and granule cell bodies in areas CA1, CA2, CA3, and dentate gyrus. Other elements of the limbic system also contain cyclic GMP-stimulated phosphodiesterase messenger RNA, including olfactory and entorhinal cortices, subiculum, and amygdala. Additional cortical regions show more diffuse expression of cyclic GMP-stimulated phosphodiesterase messenger RNA, as do the basal ganglia. Cerebellum, thalamus, and hypothalamus do not show appreciable specific labeling. These studies demonstrate the presence of cyclic GMP-stimulated phosphodiesterase messenger RNA in specific regions of the rat brain, and suggest that the cyclic GMP-stimulated phosphodiesterase might modulate neuronal activity by regulating intracellular cyclic AMP levels in response to changes in intracellular cyclic GMP levels.
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PMID:A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly expressed in the limbic system of the rat brain. 830 78

Inhibitory synapses on Purkinje cells show synaptic plasticity such as rebound potentiation (RP), which seems to contribute to refined information processing in the cerebellar cortex. Recent progress in the study on regulation mechanism of RP is reported. RP is induced by depolarization of a Purkinje cell and expressed as the increased postsynaptic responsiveness to GABA. RP might work as a homeostatic mechanism to maintain activity of a Purkinje cell sensing the strength of heterosynaptic excitatory inputs. However, there is a homosynaptic mechanism to regulate RP. RP is suppressed by the GABAergic transmission occurring during depolarization. Elaborate molecular regulation mechanism of RP induction, including GABA(B) receptors, Ca(2+), cyclic adenosine 3',5'-monophosphate (cAMP), kinases such as Ca(2+)- and calmodulin-dependent kinase II and protein kinase A, and protein phosphatases such as PP1 and PP2B, has been clarified. Application of systems biological analyses combined with electrophysiological experiments has revealed a critical role of phosphodiesterase 1 in determination of the Ca(2+) signal to induce RP.
Cerebellum 2012 Jun
PMID:Regulation of inhibitory synaptic plasticity in a Purkinje neuron. 2209 Mar 65