Noradrenergic stimulation of BDNF synthesis in astrocytes: Mediation via α1- and β1/β2-adrenergic receptors

NA (1 μM) elevates BDNF levels by four-fold after 6 h of incubation. Its stimulation was partly inhibited by either the β1-adrenergic antagonist atenolol, the β2-adrenergic antagonist ICI 118,551, or by the α1-adrenergic antagonist prazosin, while the α2-adrenergic antagonist yohimbine showed no effect. BDNF levels in astrocytes were increased by the specific β1-adrenergic agonist dobutamine and the β2-adrenergic agonist salbutamol, as well as by adenylate cyclase activation (by forskolin) and PKA activation (by dBcAMP). However, none of the tested agonists or mediators of the intracellular β-adrenergic pathways were able to reach the level of NA's stimulatory effect. BDNF cellular levels were also elevated by the α1-adrenergic agonist methoxamine, but not by the α2-adrenergic agonist clonidine. The increase in intracellular Ca2+ by ionophore A23187 showed no effect, whereas PKC activation by phorbol 12-myristate 13-acetate (TPA) potently stimulated BDNF levels in the cells. The methoxamine-stimulated BDNF synthesis was inhibited by desensitizing pretreatment with TPA, indicating that the α1-stimulation was mediated via PKC activation. In conclusion, the synthesis of astrocytic BDNF stimulated by noradrenergic neuronal activity is an adaptable process using multiple types (α1 and β1/β2) of adrenergic receptor activation.