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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Blotting, Western
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Cell Differentiation / drug effects
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Cells, Cultured
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Culture Media
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / metabolism
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Cyclic AMP / pharmacology*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology*
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Immunohistochemistry
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Insulin-Like Growth Factor I / antagonists & inhibitors*
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Insulin-Like Growth Factor I / pharmacology*
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Isoquinolines / pharmacology
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Mitogen-Activated Protein Kinases / metabolism
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Myelin Basic Protein / biosynthesis
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Oligodendroglia / drug effects*
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Phosphatidylinositol 3-Kinases / metabolism
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Rats
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Rats, Sprague-Dawley
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Substrate Specificity
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Sulfonamides / pharmacology
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Thionucleotides / pharmacology
Substances
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Culture Media
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Enzyme Inhibitors
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Isoquinolines
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Myelin Basic Protein
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Sulfonamides
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Thionucleotides
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adenosine-3',5'-cyclic phosphorothioate
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Insulin-Like Growth Factor I
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Cyclic AMP
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Phosphatidylinositol 3-Kinases
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide