Effects of adenylyl cyclase-linked neuropeptides on the expression of ciliary neurotrophic factor-mRNA in cultured astrocytes.
Ciliary neurotrophic factor (CNTF) is a molecule which has profound effects on various neural cell types. In the central nervous system, expression of CNTF-mRNA is highly concentrated in olfactory bulb. In the present study, we examined the regulatory mechanism of CNTF-mRNA expression in cultured astrocytes from newborn rat brain. Cultured astrocytes from new born rat brain expressed CNTF-mRNA at levels comparable to the level in olfactory bulb in vivo. Treatment of the astrocytes with forskolin, an activator of adenylyl cyclase, led to a decrease of CNTF-mRNA level. The effect of forskolin was mimicked by cAMP-linked agonists, such as VIP, PACAP, isoproterenol and dopamine. Cycloheximide, an inhibitor of protein synthesis, did not abolish the forskolin-induced decrease of CNTF-mRNA. Measurement of the half-life of CNTF-mRNA in the presence of actinomycin D, an inhibitor of transcription, indicated that the degradation of CNTF-mRNA is not destabilized by the forskolin-treatment. These data taken together suggest that the cAMP-induced suppression of CNTF-mRNA is mainly caused by the inhibition of CNTF gene transcription.
Nagao
H
H
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Matsuoka
I
I
Kurihara
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D020934:Ciliary Neurotrophic Factor; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000166:cytology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D020934:Ciliary Neurotrophic Factor; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D003609:Dactinomycin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D003513:Cycloheximide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004298:Dopamine