7-OH-DPAT-induced inhibition of norepinephrine release in PC12 cells

The purpose of this study was to investigate mechanisms of suppression of norepinephrine release by 7OH-DPAT, a dopamine D-2/D-3 receptor agonist, in PC12 cells pretreated with nerve growth factor (NGF). 7-OH-DPAT caused inhibition of basal and K+-evoked norepinephrine release, which could be blocked by pretreatment with raclopride, a D-2/D-3 receptor antagonist. Moreover, dopamine D-2 and D-3 receptors were identified by immunocytochemistry. Expression of D-2, D-3, and D-4 mRNAs and their proteins were detected using RT-PCR and immunoblotting. Furthermore, 7-OH-DPAT produced no change in cGMP levels; however, 7-OH-DPAT inhibited forskolin-stimulated cAMP accumulation that was antagonized by pretreatment with raclopride. In addition, 7-OH-DPAT inhibited carbachol-induced Ca2+ transient, conversely, 7-OH-DPAT had no effect on 4-aminopyridine-induced Ca2+ transient. Taken together, suppression of cAMP accumulation and calcium mobilization by 7-OH-DPAT is involved in the inhibition of norepinephrine release through activation of dopamine D-2/D-3 receptors. Copyright (C) 2004 S. Karger AG, Basel.