Neurotropic pyrimidine heterocyclic compounds. II. Effects of novel neurotropic pyrimidine derivatives on astrocytic morphological differentiation.
Astrocytes play an important role in supporting nerve regeneration after brain injuries. In this study, the effects of novel neurotropic synthesized pyrimidine compounds on astrocytic morphological differentiation were examined. Treatment of protoplasmic cultured astrocytes with 2-piperidino-5,6-dihydro-7-methyl-6-oxo(7 H)pyrrolo[2,3-d]pyrimidine maleate (MS-430) and the related compounds caused astrocytic process formation in 60 min. The morphology of MS-430-treated cells was similar to that of dibutyryl cAMP (DBcAMP)-treated cells. The astrocytic process formation by MS-430 was observed within 60 min and the maximum effect was obtained at the drug concentration of 0.5-1.0 mM. Rhodamine-phalloidin staining showed that astrocytic cytoskeletal actin was reorganized by MS-430 and DBcAMP. MS-430 did not increase cAMP accumulation in cultured astrocytes. These results suggest that the neurotropic pyrimidines induced astrocytic morphological differentiation through a cAMP-independent mechanism.
Koyama
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Awaya
A
A
Ishikawa
N
N
Fujita
S
S
Tomino
I
I
Yokoyama
K
K
Araki
S
S
Takesue
M
M
Kato
K
K
Ishiguro
M
M
Kitahara
T
T
Kihara
N
N
Baba
A
A
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C093088:MS 430; C096499:MS 818; D011743:Pyrimidines; D003994:Bucladesine