Inhibition of nerve growth factor-induced neurite outgrowth of PC12 cells by a protein kinase inhibitor which does not permeate the cell membrane.
K-252a, a protein kinase inhibitor of microbial origin, has proven to be a specific inhibitor of nerve growth factor. In this study, the effects of K-252b, the 9-carboxylic acid derivative of K-252a, on nerve growth factor-induced neurite outgrowth in PC12 cells was examined. K-252b is hydrophilic and does not permeate the cell membrane of PC12 cells, whereas K-252a clearly does. K-252b is, however, as potent as K-252a itself in inhibiting the nerve growth factor-induced neurite outgrowth. These results can be interpreted to suggest that effects of K-252b may be through surface-bound/anchored K-252b-sensitive molecules on PC12 cells.
Nagashima
K
K
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Japan.
Nakanishi
S
S
Matsuda
Y
Y
D000310:Adrenal Gland Neoplasms / Q000737:chemistry* / Q000201:enzymology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D026121:Indole Alkaloids; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010673:Pheochromocytoma / Q000737:chemistry* / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D051381:Rats
D002227:Carbazoles; D006131:Growth Inhibitors; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone