ASSESSMENT OF REGIONAL PHOSPHATE-ACTIVATED GLUTAMINASE (PAG) ACTIVITYAND KINETICS IN ADULT AND AGED FISCHER-344 RATS

The regional activity of phosphate-activated glutaminase (PAG) was ass essed in 8-month-old and 28-month-old male Fischer-344 (F344) rats fro m the temporal cortex (TCX), striatum (STR) and hippocampus (HIPP). Ba sal activity, as represented by activity in the presence of 10 mM phos phate, was decreased 23% in the TCX from aged rats compared to adults while neither the STR or HIPP exhibited age-related changes. In the pr esence of 100 mM phosphate, which will maximally stimulate PAG activit y, none of the regions displayed age-related changes although all grou ps showed increased PAG activity of 112-169% compared to corresponding values in the presence of 10 mM phosphate. Kinetic analysis revealed no alterations in the apparent affinity (Km) of PAG for glutamine in t he TCX and STR, but the Km value was increased 32% in the HIPP(255+/-1 2 muM compared to 336+/-22 muM). There were no significant changes in Vmax values. Regional variability seen in PAG basal activity and kinet ics may reflect regional differences in glutamatergic innervation or g lutamate-specific metabolic requirements of these three regions. These possibilities are discussed with regard to the aging process and neur al degeneration which may occur as a result of a dysfunctional glutama tergic system.