Ca2+-dependent modulation of GABAA and NMDA receptors by extracellular ATP: implication for function of tripartite synapse

2009 ◽  
Vol 37 (6) ◽  
pp. 1407-1411 ◽  
Author(s):  
Ulyana Lalo ◽  
Jemma Andrew ◽  
Oleg Palygin ◽  
Yuriy Pankratov
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Glial Cells ◽  
Brain Function ◽  
Aminobutyric Acid ◽  
Modern Concept ◽  
Tripartite Synapse ◽  
Regulatory Pathways ◽  
Intracellular Cascades ◽  
Kinase A

The importance of communication between neuronal and glial cells for brain function is recognized by a modern concept of ‘tripartite synapse’. Astrocytes enwrap synapses and can modulate their activity by releasing gliotransmitters such as ATP, glutamate and D-serine. One of the regulatory pathways in the tripartite synapse is mediated by P2X purinoreceptors. Release of ATP from synaptic terminals and astrocytes activates Ca2+ influx via P2X purinoreceptors which co-localize with NMDA (N-methyl-D-aspartate) and GABA (γ-aminobutyric acid) receptors and can modulate their activity via intracellular cascades which involve phosphatase II and PKA (protein kinase A).

scholarly journals Glucocorticoids and protein kinase A coordinately modulate transcription factor recruitment at a glucocorticoid-responsive unit.

1995 ◽  
Vol 15 (10) ◽  
pp. 5346-5354 ◽  
Author(s):  
M L Espinás ◽  
J Roux ◽  
R Pictet ◽  
T Grange
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cell Lines ◽  
Transcription Factor Binding ◽  
Tyrosine Aminotransferase ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
Factor Binding ◽  
Kinase A

The rat tyrosine aminotransferase gene is a model system to study transcriptional regulation by glucocorticoid hormones. We analyzed transcription factor binding to the tyrosine aminotransferase gene glucocorticoid-responsive unit (GRU) at kb -2.5, using in vivo footprinting studies with both dimethyl sulfate and DNase I. At this GRU, glucocorticoid activation triggers a disruption of the nucleosomal structure. We show here that various regulatory pathways affect transcription factor binding to this GRU. The binding differs in two closely related glucocorticoid-responsive hepatoma cell lines. In line H4II, glucocorticoid induction promotes the recruitment of hepatocyte nuclear factor 3 (HNF3), presumably through the nucleosomal disruption. However, the footprint of the glucocorticoid receptor (GR) is not visible, even though a regular but transient interaction of the GR is necessary to maintain HNF3 binding. In contrast, in line FTO2B, HNF3 binds to the GRU in the absence of glucocorticoids and nucleosomal disruption, showing that a "closed" chromatin conformation does not repress the binding of certain transcription factors in a uniform manner. In FTO2B cells, the footprint of the GR is detectable, but this requires the activation of protein kinase A. In addition, protein kinase A stimulation also improves the recruitment of HNF3 independently of glucocorticoids and enhances the glucocorticoid response mediated by this GRU in an HNF3-dependent manner. In conclusion, the differences in the behavior of this regulatory sequence in the two cell lines show that various regulatory pathways are integrated at this GRU through modulation of interrelated events: transcription factor binding to DNA and nucleosomal disruption.

Glucose and forskolin regulate IAPP gene expression through different signal transduction pathways

2001 ◽  
Vol 281 (5) ◽  
pp. E938-E945 ◽  
Author(s):  
Wei-Qun Ding ◽  
Eileen Holicky ◽  
Laurence J. Miller
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Β Cell ◽  
Regulatory Pathways ◽  
Gene Assay ◽  
Kinase A

Molecular mechanisms for the regulation of islet amyloid polypeptide (IAPP) gene expression remain unclear. In the present study, we investigated the effects of glucose and forskolin on IAPP gene regulation in the INS-1 islet β-cell line. Both glucose and forskolin increased the level of expression of this gene, as measured by Northern blot analysis, and increased IAPP gene transcription in a time- and concentration-dependent manner, as demonstrated in a reporter gene assay. Although inhibition of protein kinase A activity with H-89 eliminated the effect of forskolin on this gene, the glucose effect was unaffected. This supported the predominant use of a protein kinase A-independent signaling pathway for glucose regulation of the IAPP gene. Electrophoretic mobility shift assay further indicated that glucose and forskolin regulated expression of this gene by targeting different elements of the promoter. Mutation of the cAMP regulatory element flanking the IAPP coding region resulted in the loss of most of the forskolin-stimulated IAPP gene promoter activity, whereas glucose-enhanced IAPP gene transcription was unaffected. These results demonstrate parallel and distinct regulatory pathways involved in glucose- and forskolin-induced IAPP gene expression in this model β-cell system.

Cholecystokinin-2 receptors couple to cAMP–protein kinase A to depress excitatory synaptic currents in rat nucleus accumbens in vitro

2006 ◽  
Vol 84 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Samuel B. Kombian ◽  
Kethireddy V.V. Ananthalakshmi ◽  
Subramanian S. Parvathy ◽  
Wandikayi C. Matowe
Keyword(s):  
Nucleus Accumbens ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Synaptic Depression ◽  
Aminobutyric Acid ◽  
Inward Currents ◽  
Kinase A

We recently reported that the activation of cholecystokinin-2 receptors depress evoked excitatory postsynaptic currents (EPSCs) in nucleus accumbens (NAc) indirectly through γ-aminobutyric acid (GABA) acting on γ-aminobutyric acid-B (GABAB) receptors. Here, we determined the second messenger system that couples cholecystokinin-2 receptors to the observed synaptic depression. Using in vitro forebrain slices of rats and whole-cell patch recording, we tested the hypothesis that cholecystokinin-2 receptors are coupled to cAMP and protein kinase A signaling pathway. Cholecystokinin-8S induced inward currents and depressed evoked EPSCs. Forskolin, an activator of adenylyl cyclase and rolipram that is an inhibitor of phosphodiesterase type IV, independently increased EPSC amplitude and blocked the inward current and synaptic depression induced by cholecystokinin-8S. Furthermore, the membrane-permeable cAMP analog, 8-bromo-cAMP, blocked the cholecystokinin-8S effects. H89, a protein kinase A inhibitor, also blocked cholecystokinin-8S effects. However, depression of the evoked EPSC by baclofen, a GABAB receptor agonist, was not blocked by H89 or forskolin. These findings indicate that cholecystokinin-2, but not GABAB, receptors are coupled to the adenylyl cyclase – cAMP – protein kinase A signaling pathway in the NAc to induce inward currents and cause synaptic depression.

scholarly journals Protein kinase A and Epac activation by cAMP regulates the expression of glial fibrillary acidic protein in glial cells

2016 ◽  
Vol 68 (4) ◽  
pp. 795-801 ◽  
Author(s):  
Naotoshi Sugimoto ◽  
Shinji Miwa ◽  
Hiroyuki Nakamura ◽  
Hiroyuki Tsuchiya ◽  
Akihiro Yachie
Keyword(s):  
Protein Kinase ◽  
Glial Fibrillary Acidic Protein ◽  
Protein Kinase A ◽  
Glial Cells ◽  
Morphological Changes ◽  
Phosphodiesterase Inhibitor ◽  
Acidic Protein ◽  
Camp Analog ◽  
Gfap Expression ◽  
Kinase A

Cyclic adenosine monophosphate (cAMP) controls differentiation in several types of cells during brain development. However, the molecular mechanism of cAMP-controlled differentiation is not fully understood. We investigated the role of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) on cAMP-induced glial fibrillary acidic protein (GFAP), an astrocyte marker, in cultured glial cells. B92 glial cells were treated with cAMP-elevating drugs, an activator of adenylate cyclase, phosphodiesterase inhibitor and a ? adrenal receptor agonist. These cAMP-elevating agents induced dramatic morphological changes and expression of GFAP. A cAMP analog, 8-Br-cAMP, which activates Epac as well as PKA, induced GFAP expression and morphological changes, while another cAMP analog, 8-CPT-cAMP, which activates Epac with greater efficacy when compared to PKA, induced GFAP expression but very weak morphological changes. Most importantly, the treatment with a PKA inhibitor partially reduced cAMP-induced GFAP expression. Taken together, these results indicate that cAMP-elevating drugs lead to the induction of GFAP via PKA and/or Epac activation in B92 glial cells.

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