Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic pyrethroid insecticide permethrin significantly decreased the levels of regulatory proteins (S-100 and calmodulin) in the developing CNS of tadpoles of R. cyanophlictis. Remarkable inhibition of enzymes acetylcholinesterase and choline acetylase and significant accumulation of neurotransmitter acetylcholine were observed in permethrin treated animals. Permethrin exposure significantly decreased the activity of phosphodiesterase. The results support molecular disruptions occurring due to permethrin induced toxicity. This in turn may bring about neuronal inefficiency in the treated tadpoles.
...
PMID:Insecticide induced disruptions in functioning of developing brain of Rana cyanophlictis. 145 49

The activity of glycerophosphorylcholine cholinephosphodiesterase was quantified in the diencephalon, mesencephalon, cerebral hemispheres, olfactory bulb and cerebellum postnatally for P5 until P70 of rat brain. The initially low activities gradually increase to adult levels by P30. The patterns of regional development are reminescent of those previously described for choline acetyltransferase activity. It is suggested that these may be functionally linked in neuronal cells. The activity of glycerophosphorylcholine phosphocholine phosphodiesterase was also determined and found to be similar although only one half as active as the enzyme liberating choline. The present experiments show that both the GPC phosphocholine phosphodiesterase and the GPC choline phosphodiesterase are regionally and developmentally regulated in rat brain.
...
PMID:Developmental and regional quantitation of glycerophosphorylcholine phosphodiesterase activities in rat brain. 285 7

The induction of choline acetyltransferase (ChAT) by cAMP derivatives was studied in dissociated spinal cord cultures. Dibutyryl cAMP (dbcAMP) and 8-bromo cAMP (1 mM) produced a 2-3-fold stimulation of ChAT activity in developing cultures whereas 8-bromo cGMP had no effect. A phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine, also increased (2-fold) ChAT activity in immature cultures. Significant elevations in ChAT were detected after 2 h incubation with dbcAMP. Maximum enzyme induction was observed 24 h after dbcAMP supplementation to the culture medium. Developmental studies revealed that ChAT could be induced on days 2-16 in culture. The largest induction of ChAT activity was observed on day 7 in culture. After day 19, when control enzyme activity attained levels of mature cultures, cAMP-mediated ChAT induction was no longer observed. Cycloheximide and actinomycin D blocked ChAT induction whereas basal enzyme activity remained unaffected. Culture protein content was not changed after 1-day exposure to dbcAMP. 125I-Tetanus toxin fixation after dbcAMP treatment revealed a 20% decrease from control in neuronal surface during days 7-9 in culture. These data indicated that cAMP derivatives produced a rapid increase in cholinergic expression during a specific period of development in spinal cord cultures. There appears to be specificity to this effect, as total neuronal surface does not respond in the same manner as ChAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Induction of cholinergic expression in developing spinal cord cultures. 619 65

Transcription factor, cAMP response element-binding protein (CREB), which is phosphorylated by cAMP-dependent kinase via an increase in cAMP, and regulates gene transcription by binding to the cAMP response element (CRE) on target genes. We examined age-dependent alterations in the DNA-binding activity of CREB in rat brain regions, and the effects of rolipram, a cAMP-specific phosphodiesterase (PDE) inhibitor on the CRE-binding activity by electrophoretic mobility-shift assay (EMSA). A marked age-dependent decrease in the CRE-binding activity was shown in all brain regions examined, especially in the basal forebrain, the striatum and the hippocampus. Furthermore, CRE-binding activities in the basal forebrain of both young-adult and aged rats significantly increased 2 h after rolipram administration (1 mg/kg, i.p.), and the rolipram treatment recovered the decreased CRE-binding activity in the aged rats. The saturation experiment in EMSA also revealed that rolipram reversed the decrease in the maximum CRE-bindings in the basal forebrain with aging. Since the 5' upstream region of the rat choline acetyltransferase (ChAT) gene contains CRE, and ChAT-positive neurons in the basal forebrain project to the frontal cortex and the hippocampus, rolipram may exert its previously reported ameliorating effect on the age-related reductions of ChAT activities in the frontal cortex and the hippocampus by phosphorylating CREB in the basal forebrain with activation of cAMP-dependent protein kinase via inhibition of PDE.
...
PMID:Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor. 888 54

The effects of repeated treatment of rolipram, a cAMP specific phosphodiesterase inhibitor (0.1 mg/kg/day i.p., 14 days), on several neuronal cholinergic indices, especially on those in aged rats were examined. In young-adult rats, rolipram treatment increased choline acetyltransferase (ChAT) activity (V(max)value) in the striatum as well as in thalamus + midbrain, whereas it decreased choline esterase activity in the hippocampus. The ChAT activity (V(max)value) and the M1-R binding (B(max)value) in the aged control rats were significantly reduced in all the brain regions examined, compared with the young-adult rats, but consecutive rolipram treatment ameliorated the reductions of both indices in the frontal cortex and the hippocampus to approximately the young-adult control levels. Since high membrane binding site concentrations for rolipram itself were revealed in the frontal cortex and the hippocampus, where the rolipram treatment showed ameliorating effects on the ChAT activity and the M1-R binding, the present findings indicate that repeated rolipram administration easily affects these two brain regions. Thus, repeated rolipram administration could restore both the presynaptic ChAT activity and the postsynaptic muscarinic cholinergic M1-R binding which are decreased with aging.
...
PMID:Effects of repeated administration of rolipram, a cAMP-specific phosphodiesterase inhibitor, on acetylcholinergic indices in the aged rat brain. 1537 48

Elongation of pollen tubes in pistils of Lilium longiflorum cv. Hinomoto after self-incompatible pollination was here found to be promoted by acetylcholine (ACh) and other choline derivatives, such as acetylthiocholine, l-alpha-phosphatidylcholine and chlorocholinechloride [CCC; (2-chloroethyl) trimethyl ammonium chloride]. Moreover, the elongation was promoted by neostigmine, a potent inhibitor of acetylcholinesterase (AChE; acetylcholine-decomposing enzyme) (EC 3.1.1.7.) and activities of this and choline acetyltransferase (ChAT; acetylcholine-forming enzyme) (EC 2.3.1.6.) in pistils were associated with self-incompatibility. The activity of ChAT was lower after self-incompatible as compared with cross-compatible pollination. Application of cAMP promoted ChAT activities in both cases, whereas activity of AChE in pistils after self-pollination was higher than that after cross-compatible pollination and was suppressed by cAMP in both cases. Furthermore, AChE activity was inhibited by treatment with neostigmine or heating. Our results indicate that the self-incompatibility with self-pollination is due to decrease of ACh and cAMP, causing reduction of ChAT and AC (adenylate cyclase) and concise elevation of AChE and PDE (cAMP phosphodiesterase), and therefore suppressed growth of pollen tubes.
...
PMID:Regulation of self-incompatibility by acetylcholine and cAMP in Lilium longiflorum. 1688 55

Previously, using brain slices, we reported NO-mediated cGMP synthesis in all cholinergic fibers in the rat neocortex. In order to answer the question whether this property of cholinergic fibers was present before or developed after birth, we investigated properties of NO-responsiveness of cultured cholinergic forebrain neurons. Basal forebrain neurons of E16 fetal rat were cultured. Under the conditions chosen and after one day of culturing, all cells had attained a cholinergic phenotype using choline acetyltransferase or the vesicular acetylcholine transporter molecule as markers. Between 95-99% of the cells also expressed neuronal NOS. In the presence of 1 mM IBMX, a non-selective phosphodiesterase (PDE) inhibitor, 10 microM of the NO donor diethylamine-NONOate (DEANO) increased cGMP synthesis in 80% of the cells. cGMP levels in the cultured forebrain neurons were also increased when cells were stimulated with DEANO in the presence of the selective PDE inhibitors BAY 60-7550 (PDE2), sildenafil (PDE5), or the mixed type inhibitor papaverine (PDE2,5,10). Subpopulations of cells from the basal forebrain expressed mRNA for PDE2, PDE5, and PDE9. Atropine increased cGMP levels in an NO-dependent manner in a small population of cultured forebrain cells in the presence of IBMX. In conclusion, cultured cholinergic basal forebrain neurons present a heterogeneous cell population in the magnitude of their response to NO. NO-responsiveness of the cultured cholinergic neurons is already detectable after one day of culturing and indicates that NO-sensitivity of the cholinergic neurons of the rat basal forebrain is present well before birth.
...
PMID:NO-mediated cGMP synthesis in cultured cholinergic neurons from the basal forebrain of the fetal rat. 1850 78

Inhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of PDE10A activity would have significant effects on gene expression in the striatum. A comparison of the expression profile of PDE10A knockout (KO) mice and wild-type mice after chronic PDE10A inhibition revealed altered expression of 19 overlapping genes with few significant changes outside the striatum or after administration of a PDE10A inhibitor to KO animals. Chronic inhibition of PDE10A produced up-regulation of mRNAs encoding genes that included prodynorphin, synaptotagmin10, phosphodiesterase 1C, glutamate decarboxylase 1, and diacylglycerol O-acyltransferase and a down-regulation of mRNAs encoding choline acetyltransferase and Kv1.6, suggesting long-term suppression of the PDE10A enzyme is consistent with altered striatal excitability and potential utility as a antipsychotic therapy. In addition, up-regulation of mRNAs encoding histone 3 (H3) and down-regulation of histone deacetylase 4, follistatin, and claspin mRNAs suggests activation of molecular cascades capable of neuroprotection. We used lentiviral delivery of cAMP response element (CRE)-luciferase reporter constructs into the striatum and live animal imaging of 2-{4-[-pyridin-4-yl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid (TP-10)-induced luciferase activity to further demonstrate PDE10 inhibition results in CRE-mediated transcription. Consistent with potential neuroprotective cascades, we also demonstrate phosphorylation of mitogen- and stress-activated kinase 1 and H3 in vivo after TP-10 treatment. The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease.
...
PMID:Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease. 2092 67

Recent, large-scale, genome-wide association studies (GWAS) provide a first view of the genetic fine structure of cognitive performance in healthy individuals. These studies have pooled data from up to 1.1 million subjects based on simple measures of cognitive performance including educational attainment, self-reported math ability, highest math class taken, and pooled, normalized scores from cognitive tests. These studies now allow the genome-wide interrogation of genes and pathways for their potential impact on human cognitive performance. The phosphodiesterase (PDE) enzymes regulate key cyclic nucleotide signaling pathways. Many are expressed in the brain and have been the targets of CNS drug discovery. Genetic variation in PDE1C, PDE4B and PDE4D associates with multiple measures of human cognitive function. The large size of the human PDE4B and PDE4D genes allows genetic fine structure mapping to transcripts encoding dimeric (long) forms of the enzymes. Upstream and downstream effectors of the cAMP pathway modulated by PDE4D [adenylate cyclase 1 (ADCY1), ADCY8, PRKAR1A, CREB1, or CREBBP] did not show genetic association with cognitive performance, however, genetic association was seen with brain derived neurotrophic factor (BDNF), a gene whose expression is modulated by cAMP. Notably absent was genetic association in healthy subjects to targets of CNS drug discovery designed to improve cognition in disease states by the modulation of cholinergic [acetylcholinesterase (ACHE), choline acetyltransferase (CHAT), nicotinic alpha 7 acetylcholine receptor (CHRNA7)], serotonergic (HTR6), histaminergic (HRH3), or glutamatergic (GRM5) pathways. These new data provide a rationale for exploring the therapeutic benefit of selective inhibitors of PDE1C, PDE4B and PDE4D in CNS disorders affecting cognition.
...
PMID:Genetic Association of Phosphodiesterases With Human Cognitive Performance. 3080 55

The aim of this study was to find out neuron (-like) cells in peripheral organs by cell markers in rats. Adult male Sprague-Dawley rats were anaesthetized. Their organs including brain, heart, lung, liver, kidney, stomach, duodenum, and ileum were harvested. The mRNA and protein in these organs were extracted. RNA sequencing (RNA-Seq) was carried out, and NeuN, a "specific" marker for neuronal soma, was assayed with Western blotting. The sections of the aforementioned organs were obtained after a routine fixation (4% methanal)-dehydration (ethanol)-embedding (paraffin) process. NeuN in the sections and seven non-neuronal cell lines was analyzed by immunofluorescence (IF) or immunohistochemistry (IHC). Neuronal markers, such as Eno2, NeuN (Rbfox3), choline acetyltransferase (Chat), as well as tyrosine hydroxylase (Th), and neuronal-glial markers, e.g., glial fibrillary acidic protein (Gfap), S100b, 2', 3'-cyclic nucleotide 3'-phosphodiesterase (Cnp), and other related markers, were positively expressed in all the organs at mRNA level. NeuN was further analyzed by Western blotting. The IF and IHC assays showed that NeuN-positive cells were distributed in all the peripheral tissues (mainly peri-nuclear NeuN-positive cells) though with different patterns from that in brain (nuclear NeuN-positive cells), and a NeuN-negative tissue could not be found. Especially, NeuN and Myl3 co-expressed in the cytoplasm of myocardial cells, suggesting that NeuN could possess other functions than neuronal differentiation. Also, the protein was positively expressed in seven non-neuronal cell lines. Our findings suggested that NeuN-positive cells exist widely, and without identification of its distribution pattern, the specificity of NeuN for neurons could be limited.
...
PMID:A pilot study on searching for peri-nuclear NeuN-positive cells. 3193 76


1

---