Serofendic acid promotes stellation induced by cAMP and cGMP analogs in cultured cortical astrocytes.
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.
Kume
Toshiaki
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Ito
Ryo
R
Taguchi
Ryota
R
Izumi
Yasuhiko
Y
Katsuki
Hiroshi
H
Niidome
Tetsuhiro
T
Takada-Takatori
Yuki
Y
Sugimoto
Hachiro
H
Akaike
Akinori
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007545:Isoproterenol / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000577:Amides; D002227:Carbazoles; D004224:Diterpenes; D018696:Neuroprotective Agents; D011725:Pyridines; D011758:Pyrroles; C452642:serofendic acid; C108830:Y 27632; C016276:8-bromocyclic GMP; C016658:phorbolol myristate acetate; C057416:KT 5720; D003994:Bucladesine; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate