kt-5720 and serofendic-acid

We investigated the effect of serofendic acid, a neuroprotective substance derived from fetal calf serum, on the morphological changes in cultured cortical astrocytes. Cultured astrocytes developed a stellate morphology with several processes following exposure to dibutylyl cAMP (dbcAMP), a membrane-permeable cAMP analog; 8-Br-cGMP, a membrane-permeable cGMP analog; or phorbol-12-myristate-13-acetate (PMA), a protein kinase C activator. Serofendic acid significantly accelerated the stellation induced by dbcAMP- and 8-Br-cGMP. In contrast, the PMA-induced stellation was not affected by serofendic acid. Next, we attempted to elucidate the mechanism underlying the dbcAMP-induced stellation and explore the site of action of serofendic acid. Both the stellation induced by dbcAMP and the promotional effect of serofendic acid were partially inhibited by KT5720, a specific protein kinase A (PKA) inhibitor. Furthermore, serofendic acid failed to facilitate the stellation induced by Y-27632, an inhibitor of Rho-associated kinase (ROCK). These results indicate that serofendic acid promotes dbcAMP- and 8-Br-cGMP-induced stellation and the promotional effect on dbcAMP-induced stellation is mediated at least partly by the regulation of PKA activity and not by controlling ROCK activity.

Topics: Adrenergic beta-Agonists; Amides; Animals; Astrocytes; Bucladesine; Carbazoles; Cell Shape; Cells, Cultured; Cerebral Cortex; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Diterpenes; Dose-Response Relationship, Drug; Drug Synergism; Isoproterenol; Neuroprotective Agents; Pyridines; Pyrroles; Rats; Rats, Wistar; rho-Associated Kinases; Tetradecanoylphorbol Acetate; Time Factors