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

Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons. HCN channels in V1 were classically located on distal dendrites, and enhanced cell firing. These data contrast with dlPFC, where PDE4A and HCN channels are concentrated in thin spines, and cAMP-HCN signaling gates inputs and weakens firing. These regional differences may explain why V1 neurons are more resilient than dlPFC neurons to the challenges of age and disease.
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PMID:Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex. 2935 85

The calcium-regulated phosphodiesterase 1 (PDE1) family is highly expressed in the brain, but its functional role in neurones is poorly understood. Using the selective PDE1 inhibitor Lu AF64196 and biosensors for cyclic nucleotides including a novel biosensor for cGMP, we analyzed the effect of PDE1 on cAMP and cGMP in individual neurones in brain slices from male newborn mice. Release of caged NMDA triggered a transient increase of intracellular calcium, which was associated with a decrease in cAMP and cGMP in medium spiny neurones in the striatum. Lu AF64196 alone did not increase neuronal cyclic nucleotide levels, but blocked the NMDA-induced reduction in cyclic nucleotides indicating that this was mediated by calcium-activated PDE1. Similar effects were observed in the prefrontal cortex and the hippocampus. Upon corelease of dopamine and NMDA, PDE1 was shown to down-regulate the D1-receptor mediated increase in cAMP. PDE1 inhibition increased long-term potentiation in rat ventral striatum, showing that PDE1 is implicated in the regulation of synaptic plasticity. Overall, our results show that PDE1 reduces cyclic nucleotide signaling in the context of glutamate and dopamine coincidence. This effect could have a therapeutic value for treating brain disorders related to dysfunctions in dopamine neuromodulation.
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PMID:Phosphodiesterase 1 Bridges Glutamate Inputs with NO- and Dopamine-Induced Cyclic Nucleotide Signals in the Striatum. 3087 87

The present study aims to evaluate the involvement of N-methyl-d-aspartate receptor and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in antidepressant-like effects of Yueju pill (YJ), a Chinese herbal medicine. The immobility time in tail suspension test (TST) and forced swim test (FST) was used to assess the antidepressant effects. Prior administration of L-arginine (750 mg/kg, intraperitoneal [i.p.]), a NO synthase substrate that enhances NO signaling or sildenafil (5 mg/kg, i.p.), a phosphodiesterase 5 inhibitor that enhances cGMP, blunted the antidepressant-like activity of YJ (2.7 g/kg, i.g.). Co-treatment of ineffective dose of YJ (1.35 g/kg, i.g.) with one of the reagents that suppress the NO/cGMP signaling, including methylene blue (10 mg/kg, i.p.), an inhibitor of NO synthase; 7-NI (7-nitroinidazole, 30 mg/kg, i.p.), an nNOS specific inhibitor; L-NAME (10 mg/kg, i.p.), a non-specific inhibitor of NO synthase; and MK-801 (0.05 mg/kg, i.p.), an NMDA receptor antagonist, reduced the immobility time in TST and FST, compared with those in vehicle or single drug treatment groups. Neither above drugs alone or co-administrated with YJ affected locomotor activity or anxiety behavior in open field test. Thus, our results suggest that the antidepressant-like action of YJ may depend on the inhibition of NMDA/NO/cGMP pathway.
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PMID:NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice. 3146 74


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