Increased phosphorylation of the NR1 subunit of the NMDA receptor following cerebral ischemia

The effects of transient cerebral ischemia on phosphorylation of the NR1 su bunit of the NMDA receptor by protein kinase C (PKC) and protein kinase A ( PKA) were investigated. Adult rats received 15 min of cerebral ischemia fol lowed by various times of recovery. Phosphorylation was examined by immunob lotting hippocampal homogenates with antibodies that recognized NR1 phospho rylated on the PKC phosphorylation sites Ser890 and Ser896, the PKA phospho rylation site Ser897, or dually phosphorylated on Ser896 and Ser897. The ph osphorylation of all sites examined increased following ischemia. The incre ase in phosphorylation by PKC was greater than by PKA. The ischemia-induced increase in phosphorylation was predominantly associated with the populati on of NR1 that was insoluble in 1% deoxycholate. Enhanced phosphorylation o f NR1 by PKC and PKA may contribute to alterations in NMDA receptor functio n in the postischemic brain.