Nonselective inhibition by antisense oligonucleotides of cytosine arabinoside action.

Antisense oligonucleotides can be used in cell cultures to inhibit biosynthesis of neurotransmitter receptors. Hence, they operate as highly specific pharmacological antagonists. In obtaining a pure neuronal primary culture the suppression of non-neuronal cell proliferation is required; usually 1-beta-D-arabinofuranosylcytosine (AraC) is used. We report that in primary cultures of rat cerebellar cells, oligonucleotides, targeted to: (1) glutamate receptor, (2) the seven transmembrane spanning region of receptors coupled to GTP binding proteins, and (3) beta-adrenergic receptor kinase, nonspecifically inhibit the cell incorporation of 3H-AraC and curtail its antiproliferative action. This nonspecific action might occur at the level of the mechanism of action of AraC and should be taken into account when antisense probes as pharmacological antagonists are used.