DIFFERENTIAL AND COORDINATED REGULATION OF EXPRESSION OF NOREPINEPHRINE TRANSPORTER IN CATECHOLAMINERGIC CELLS IN CULTURE

The norepinephrine transporter (NET) terminates noradrenergic neurotra nsmission at synapse by high-affinity sodium-dependent reuptake into p resynaptic terminals, and thus serves as a marker of differentiation o f noradrenergic neurons. In the present study, we studied the regulato ry mechanism of the expression of NET-mRNA in cultured neurons from ne wborn rat superior cervical ganglia (SCG) and in clonal rat pheochromo cytoma cells (PC12). SCG neurons in culture expressed a high level of NET-mRNA, which was further increased 2.5-5 fold from day 1 to day 13. Treatment of SCG neurons with the cholinergic differentiation factor (CDF)/leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), neurokines known to induce the switch from adrenergic to chol inergic phenotype in SCG neurons, led to the suppression of the level of NET-mRNA in a concentration dependent manner, concomitantly with th e suppression of mRNA for tyrosine hydroxylase (TH), an adrenergic mar ker enzyme in cultured SCG neurons. On the other hand, retinoic acid, a compound which is also known to increase the expression of choline a cetyltransferase, a cholinergic marker enzyme, and suppress the expres sion of TH in the cultured SCG neurons and PC12 cells, rather increase d the level of NET-mRNA in these two cell populations. Alterations of the Na+-dependent norepinephrine transport activity which paralleled t he changes in the NET-mRNA levels were confirmed by the [H-3]norepinep hrine uptake assay. These results indicate that cell extrinsic factors regulate the expressions of NET and TH genes by a common as well, as by distinct mechanisms. (C) 1997 Elsevier Science B.V.