Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons.
The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.
Pezet
Sophie
S
King's College London, Center for Age Related Diseases, Wolfson Wing, Guy's Campus, London Bridge, London SE1 1UL, UK. sophie.pezet@kcl.ac.uk
Spyropoulos
Achillefs
A
Williams
Robert J
RJ
McMahon
Stephen B
SB
D000469:Alkaline Phosphatase / Q000494:pharmacology; D000704:Analysis of Variance; D000730:Androstadienes / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D017630:Connexins; D003720:Densitometry / Q000379:methods; D003952:Diagnostic Imaging / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D007473:Ion Channels / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009186:Myelin Sheath / Q000378:metabolism; D009407:Nerve Block / Q000379:methods; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012694:Serine / Q000378:metabolism; D050916:TRPV Cation Channels; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D000779:Anesthetics, Local; D002867:Chromones; D017630:Connexins; D004791:Enzyme Inhibitors; D007473:Ion Channels; D037102:Lectins; D009025:Morpholines; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014404:Tubulin; C479937:pannexin 2, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D013779:Tetrodotoxin; D012694:Serine; D011189:Potassium Chloride; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D000077191:Wortmannin