scholarly journals Intracellular Sodium Regulates Opioid Signalling in Peripheral Neurons

2017 ◽  
Author(s):  
Alexandros H. Kanellopoulos ◽  
Jing Zhao ◽  
Edward C. Emery ◽  
John N Wood
Keyword(s):  
Protein Kinase ◽  
Sodium Channel ◽  
Protein Kinase A ◽  
Fold Increase ◽  
Intracellular Sodium ◽  
Peripheral Neurons ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Kinase A

AbstractOpioid receptors signal more effectively in sensory neurons from pain-free mice lacking the voltagegated sodium channel Nav1.7. Type-A GPCRs are known to be regulated through a specific sodium binding site, the occupancy of which diminishes agonist binding. We have used an electrophysiological assay of Protein Kinase A activity to examine the role of intracellular sodium on opioid signalling. Phosphorylation of sodium channel Nav1.8 by activation of Protein Kinase A with db-cAMP is unaffected by altered intracellular sodium. By contrast, there is a dose-dependent inhibition of fentanyl action on Nav1.8 currents when intracellular sodium is increased from 0 mM to 20 mM. Fentanyl shows a 50% loss of activity and 80-fold increase in EC50 with 20 mM intracellular sodium. These data demonstrate that altered intracellular sodium levels modulate opioid receptor signalling.

Intracellular Ca2+ regulates responsiveness of cardiac L-type Ca2+ current to protein kinase A: role of calmodulin

2004 ◽  
Vol 286 (1) ◽  
pp. H186-H194 ◽  
Author(s):  
Kenneth B. Walsh ◽  
Qi Cheng
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ventricular Myocytes ◽  
External Solution ◽  
Inhibitory Peptide ◽  
Dependent Inhibition ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Kinase A

The goal of this study was to determine whether the protein kinase A (PKA) responsiveness of the cardiac L-type Ca2+ current ( ICa) is affected during transient increases in intracellular Ca2+ concentration. Ventricular myocytes were isolated from 3- to 4-day-old neonatal rats and cultured on aligned collagen thin gels. When measured in 1 or 2 mM Ca2+ external solution, the aligned myocytes displayed a large ICa that was weakly regulated (20% increase) during stimulation of PKA by 2 μM forskolin. In contrast, application of forskolin caused a 100% increase in ICa when the external Ca2+ concentration was reduced to 0.5 mM or replaced with Ba2+. This Ca2+-dependent inhibition was also observed when the cells were treated with 1 μM isoproterenol, 100 μM 3-isobutyl-1-methylxanthine, or 500 μM 8-bromo-cAMP. The responsiveness of ICa to PKA was restored during intracellular dialysis with a calmodulin (CaM) inhibitory peptide but not during treatment with inhibitors of protein kinase C, Ca2+/CaM-dependent protein kinase, or calcineurin. Adenoviral-mediated expression of a CaM molecule with mutations in all four Ca2+-binding sites also increased the PKA sensitivity of ICa. Finally, adult mouse ventricular myocytes displayed a greater response to forskolin and cAMP in external Ba2+. Thus Ca2+ entering the myocyte through the voltage-gated Ca2+ channel regulates the PKA responsiveness of ICa.

Regulation of arginine vasopressin mRNA in rat fetal hypothalamic cell culture. Role of protein kinases and glucocorticoids

1993 ◽  
Vol 10 (1) ◽  
pp. 51-57 ◽  
Author(s):  
S-B Hu ◽  
L A Tannahill ◽  
S L Lightman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Protein Kinase A ◽  
Arginine Vasopressin ◽  
In Situ Hybridization Histochemistry ◽  
Kinase C ◽  
Kinase A

ABSTRACT Studies have been performed to investigate the regulation of arginine vasopressin (AVP) mRNA expression in fetal hypothalamic cultures. AVP mRNA-positive neurones were identified by in-situ hybridization histochemistry, and changes in mRNA expression were quantitated by nuclease protection assay. Both protein kinase C and protein kinase A activators increased the expression of AVP mRNA, in contrast to dexamethasone, which inhibited the responses to both protein kinase C and protein kinase A activation.

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