myelin-basic-protein and adenosine-3--5--cyclic-phosphorothioate

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.

Topics: Animals; Animals, Newborn; Blotting, Western; Cell Differentiation; Cells, Cultured; Culture Media; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Enzyme Activation; Enzyme Inhibitors; Immunohistochemistry; Insulin-Like Growth Factor I; Isoquinolines; Mitogen-Activated Protein Kinases; Myelin Basic Protein; Oligodendroglia; Phosphatidylinositol 3-Kinases; Rats; Rats, Sprague-Dawley; Substrate Specificity; Sulfonamides; Thionucleotides