EFFECTS OF ADENYLYL CYCLASE-LINKED NEUROPEPTIDES ON THE EXPRESSION OFCILIARY NEUROTROPHIC FACTOR-MESSENGER-RNA IN CULTURED ASTROCYTES

Ciliary neurotrophic factor (CNTF) is a molecule which has profound ef fects on various neural cell types. In the central nervous system, exp ression of CNTP-mRNA is highly concentrated in olfactory bulb. In the present study, we examined the regulatory mechanism of CNTF-mRNA expre ssion in cultured astrocytes from newborn rat brain. Cultured astrocyt es 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 CNT F-mRNA level. The effect of forskolin was mimicked by cAMP-linked agon ists, such as VIP, PACAP, isoproterenol and dopamine. Cycloheximide, a n inhibitor of protein synthesis, did not abolish the forskoln-induced decrease of CNTF-mRNA. Measurement of the half-life of CNTF-mRNA in t he presence of actinomycin D, an inhibitor of transcription, indicated that the degradation of CNTF-mRNA is not destabilized by the forskoli n-treatment. These data taken together suggest that the cAMP-induced s uppression of CNTF-mRNA is mainly caused by the inhibition of CNTF gen e transcription.