Opposite effects of two PKA inhibitors on cAMP inhibition of IGF-I-induced oligodendrocyte development: a problem of unspecificity?

Brain Res. 2007 Oct 31;1178:1-11. doi: 10.1016/j.brainres.2007.07.018. Epub 2007 Aug 22.

Abstract

The stimulatory effect of insulin-like growth factor I (IGF-I) on myelin basic protein (MBP) expression, a parameter for oligodendrocyte development, is mediated by the MAPK and PI3K signaling pathways. We have previously shown that the second messenger cAMP inhibits IGF-I-induced MAPK activation as well as MBP expression. We also showed that the PKA inhibitor Rp-cAMPS reverted the cAMP effect on IGF-I-induced MBP without affecting the cAMP effect on IGF-I-induced MAPK activation. Here we report that, in contrast to Rp-cAMPS, H89 (a PKA inhibitor structurally non-related to Rp-cAMPS) enhances both the inhibitory effect of cAMP on IGF-I-induced MBP expression and the inhibitory effect of cAMP on IGF-I-induced MAPK activation. Likewise, H89 is capable of inhibiting the IGF-I-induced MAPK activation in the absence of PKA stimulation. Thus, we hypothesize that an unspecific action of H89 on a target located upstream MAPK could account for the discrepancies between the effects elicited by Rp-cAMPS and H89.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Culture Media
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology*
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Insulin-Like Growth Factor I / pharmacology*
  • Isoquinolines / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism
  • Myelin Basic Protein / biosynthesis
  • Oligodendroglia / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Substrate Specificity
  • Sulfonamides / pharmacology
  • Thionucleotides / pharmacology

Substances

  • Culture Media
  • Enzyme Inhibitors
  • Isoquinolines
  • Myelin Basic Protein
  • Sulfonamides
  • Thionucleotides
  • adenosine-3',5'-cyclic phosphorothioate
  • Insulin-Like Growth Factor I
  • Cyclic AMP
  • Phosphatidylinositol 3-Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide