Age-dependent differences in glutamate-induced phosphorylation systems in rat hippocampal slices

Glutamate receptor induced changes in the activity of different phosphoryla tion systems were measured in hippocampal slices from 12- and 56-day-old ra ts, by determining the endogenous phosphorylation of 2.5% perchloric acid ( PCA) soluble proteins. We identified among these proteins an 85, 80 kDa and the tau protein as specific substrates for protein kinase A (PKA), MARCKS, and neurogranin as specific substrates for protein kinase C (PKC), and pro staglandin-D-synthase as substrate for casein kinase II (CKII). In addition , a 35 kDa protein was phosphorylated by calcium/calmodulin dependent kinas e Il and protein kinase C and a 21 kDa protein was a substrate for all inve stigated kinases. The basal endogenous phosphorylation of 2.5% PCA soluble proteins changed d uring development qualitatively and quantitatively. Thus, the phosphorylati on degree of nearly all proteins declines during maturation. Activation of mGluR induced an increased phosphorylation of PKA, PKC, and CKII substrates in hippocampal slices from 12-day-old rats, but in slices of 56-day-old ra ts only PKA and to a lower extent PKC substrates were affected. In contrast , stimulation of NMDA receptors led to an enhancement of CKII and PKA depen dent phosphorylation only in slices of young animals, whereas the endogenou s phosphorylation of some proteins in adult slices was actually decreased. These data showing developmental changes in the coupling of metabotropic an d ionotropic glutamate receptors to different phosphorylation systems are d iscussed in the light of altered physiological properties of the mature hip pocampus. Hippocampus 1999;9:173-185. (C) 1999 Wiley-Liss, Inc.