RO 31-8220 and RO 31-7549 show improved selectivity for protein kinase C over staurosporine in macrophages.
Two new potent protein kinase C inhibitors, RO 31-8220 and RO 31-7549, and staurosporine were found to inhibit dose-dependently the phorbol ester-induced formation of prostaglandin E2 and superoxide in cultured liver macrophages. Prostaglandin E2 formation from exogenously added arachidonate was not affected by these compounds. The zymosan-induced formation of inositol phosphates was decreased by simultaneous addition of phorbol ester and was enhanced by prior desensitization of protein kinase C indicating that protein kinase C negatively modulates phospholipase C activation in these cells. While staurosporine suppressed almost totally the zymosan-induced formation of inositol RO 31-8220 and RO 31-7549 inhibited the protein kinase C-mediated effect on inositol phosphate formation, only. Phagocytosis of zymosan was not affected by RO 31-8220 and RO 31-7549 but was decreased by staurosporine. These results demonstrate that two new potent protein kinase C inhibitors, RO 31-8220 and RO 31-7549, are more selective in their actions as staurosporine and are useful tools to determine an involvement of protein kinase C in cellular systems.
Dieter
P
P
Biochemisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Fitzke
E
E
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D007211:Indoles; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology*; D008301:Maleimides; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220; C064755:Ro 31-7549