scholarly journals Protein Kinase A–dependent Spinal α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionate–receptor Trafficking Mediates Capsaicin-induced Colon-Urethra Cross-organ Reflex Sensitization

2011 ◽  
Vol 114 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Hsien-Yu Peng ◽  
Chao-Hsiang Chang ◽  
Shin-Jei Tsai ◽  
Cheng-Yuan Lai ◽  
Kwong-Chung Tung ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Membrane Fraction ◽  
Cyclic Adenosine Monophosphate ◽  
Fold Increase ◽  
Adenosine Monophosphate ◽  
Human Thyroid ◽  
Anchoring Protein ◽  
Ampar Trafficking ◽  
Kinase A

Background Intracellular redistribution of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptors (AMPARs) is known to be induced by natural painful stimulation. We tested the hypothesis that that protein kinase A (PKA)-dependent AMPAR trafficking underlies the development of N-methyl-d-aspartate receptor-mediated cross-organ sensitization in vivo. Methods We recorded urethra reflex activity and analyzed immunoblotting of lumbosacral (L6-S2) dorsal horn (DH) tissue obtained from animal preparations after intrathecal 8-bromo-cyclic adenosine monophosphate injection or intracolonic instillation with 8-methyl-N-vanillyl-trans-6-nonenamide (capsaicin). Results Intrathecal 8-bromo-cyclic adenosine monophosphate (300 μM, 10 μl) induced reflex potentiation (81.85 ± 22.21 spikes/stimulation) and increased the number of AMPAR Glu receptor 1 subunits in the membrane fraction of DH (1.8-fold increase vs. control). This process was prevented by pretreatment with the PKA inhibitor N-[2- ((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide(10 μM, 10 μl, 2.7 ± 0.8 [mean ± SE] spikes/stimulation) and human thyroid A kinase-anchoring protein (10 μM, 10 μl, 11.5 ± 4.8 spikes/stimulation), an inhibitor of PKA and PKA-A kinase-anchoring protein interactions. Intracolonic capsaicin instillation sensitized the urethra reflex (137.2 ± 62.4 spikes/stimulation) and, relative to control, simultaneously provoked an increase (2.9-fold) in the membrane fraction and a decrease (0.9-fold) in the cytosolic fraction of Glu receptor 1 subunits in DH. Inhibition of PKA activity and disruption of PKA-A kinase-anchoring protein interaction in the DH (2.0 ± 0.6 and 16.7 ± 2.8 spikes/stimulation, respectively) are sufficient to prevent capsaicin-dependent reflex sensitization and AMPAR trafficking in the membrane fraction (0.6- and 0.5-fold increase capsaicin). Conclusion Delivery of AMPAR-containing Glu receptor 1 subunits to the membranes of lumbosacral DH neurons through a PKA-dependent pathway contributes to noxious stimulation-induced synaptic strengthening, which plays roles in colon-urethra reflex sensitization.

scholarly journals Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP

2007 ◽  
Vol 176 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Jianzhong Han ◽  
Liang Han ◽  
Priyanka Tiwari ◽  
Zhexing Wen ◽  
James Q. Zheng
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Growth Cone ◽  
Regulatory Protein ◽  
Cyclic Adenosine Monophosphate ◽  
Spatial Localization ◽  
Adenosine Monophosphate ◽  
Type Ii ◽  
Regulation Of Growth ◽  
Kinase A

The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and guidance by cAMP.

scholarly journals Protein Kinase Inhibitor Peptide as a Tool to Specifically Inhibit Protein Kinase A

2020 ◽  
Vol 11 ◽  
Author(s):  
Chong Liu ◽  
Ping Ke ◽  
Jingjing Zhang ◽  
Xiaoying Zhang ◽  
Xiongwen Chen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase Inhibitor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Protein Kinase Inhibitor ◽  
The Body ◽  
Specific Method ◽  
Inhibitor Peptide ◽  
Kinase A

The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.

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