Effects of adenylyl cyclase‐linked neuropeptides on the expression of ciliary neurotrophic factor‐mRNA in cultured astrocytes

Abstract

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.