PKA phosphorylates NR1 subunits,65 which leads to increased NMDA receptor function.74 Activation of dopamine D1 receptors induces PKA-mediated phosphorylation of NR1 subunits and subsequent phosphorylation and activation of the transcription factor CREB in rat striatal neurons.75 D1 receptor-mediated CREB phosphorylation is blocked by the NMDA receptor antagonist MK801 but not by either of the MEK inhibitors PD98059 or U0126.75 However, PKA can indirectly activate ERK by facilitating the activation of B-Raf through the small G-protein Rap1; B-Raf then phosphorylates and activates MEK.60 Thus, activation of α7 nACh receptors by nicotine stimulates the ERK pathway in a PKA-dependent manner in mouse hippocampal neurons.76
