NAD(P)H:quinone oxidoreductase (QR) and glutathione‐S‐transferases (GSTs) are among the enzymes believed to protect an organism against oxidative stress. To test if redox‐cycling compounds regulate the expression of these enzymes in cells of neural origin, primary cultures of rat cerebellar neurons and glia were treated with tert‐butylhydroquinone (tBHQ) and hydroquinone (HQ). Basal levels of endogenous QR and GST activity were significantly greater in glia than neurons; and QR, GSTP1, and A3 were increased in glial but not neuronal cultures by treatment with tBHQ and HQ. A possible role for protein kinase C (PKC) in the tBHQ‐mediated increase in QR and GST was evaluated by activating PKC with phorbol 12‐myristate 13‐acetate or inhibiting PKC with bisindolylmaleimide I. PKC was not involved in maintaining basal expression or mediating the increased expression of GST or QR by tBHQ. Transcriptional activation of QR and rGSTP1 by tBHQ could be mediated through a common responsive element present in the 5′‐flanking region of both genes, the antioxidant/electrophile responsive element (ARE/EpRE). Transient transfection of the glial cultures with rGSTP1‐ or rQR1‐ARE/EpRE‐luciferase reporter constructs demonstrated that tBHQ transcriptionally activates the ARE/EpRE. Thus, the increased expression of genes regulated by the ARE/EpRE in cells of the central nervous system may provide protection against oxidative stress. GLIA 25:131–142, 1999. © 1999 Wiley‐Liss, Inc.

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A substantial body of evidence shows the capacity of the dopamine D3 receptor to couple functionally to G proteins when expressed in an appropriate milieu in heterologous expression systems. In these systems, activation of D3 receptors inhibits adenylate cyclase, modulates ion flow through potassium and calcium channels, and activates kinases, most notably mitogen-activated protein kinase. Coupling to Gi/Go is implicated in many of these effects, but other G proteins may contribute. Studies with chimeric receptors implicate the third intracellular loop in the mediation of agonist-induced signal transduction. Finally, D3-preferring drugs modulate expression of c-fos in neuronal cultures and brain. Signaling mechanisms of the D3 receptor in brain, however, remain to be definitively determined.

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