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Abstract
The vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT)
are encoded by genes organized in a single gene locus, and coregulation of the transcription
of the two genes has been repeatedly reported in cholinergic tissues. In the present
study, different stimuli were used to induce the differentiation of the hybridoma
cells NG108-15 and we examined their effects on the modulation of VAChT and ChAT expression
at the mRNA and protein levels. All agents upregulated the VAChT and ChAT mRNA levels,
but to a different extent. ChAT activity was increased by retinoic acid, dexamethasone,
and dibutyrylcyclic AMP (dbcAMP), and a synergistic effect was observed with a combined
dexamethasone and dbcAMP treatment. Nonetheless, no changes in the VAChT protein level
could be observed, as judged from ligand binding studies as well as from immunochemical
detection. Hemicholinium-3-sensitive choline uptake, hemicholinium-3 binding, and
acetylcholine content were increased by differentiating agents, with a rank order
of potency comparable to their effects on ChAT activity. Prominent changes were observed
in the expression of vesicular protein markers, particularly with the associated treatment
dexamethasone and dbcAMP. Thus, it appears that although the different stimuli we
have been using are able to stimulate neuronal features and activate the transcription
of cholinergic genes, they did not contrive to increase the level of VAChT protein
in these cells.