In vivo and in vitro effects of hyperglycemia on Na+ -K+, Ca+2, Mg+2-dependent ATPases activity in brain synaptosomes of aging rats.

Cerebral metabolism of glucose, one of the determinants of tissue ATP level, is crucial for the CNS function. The activity of P-type pumps: Na(+), K(+)-ATPase, Ca(+2)-ATPase and Mg(+2)-ATPase were examined in rat brain synaptosomes to determine if changes in the enzyme activity related to aging are potentially associated with alterations in glucose homeostasis. Male Wistar rats (newborn, 3- and 18-month-old) were sacrificed by decapitation and synaptic plasma membranes were isolated from brains. In vivo study demonstrated that 18-month-old rats were characterized by hyperglycemia, hyperinsulinemia and increased total antyoxidative status (TAS) level. These conditions had a different impact on activities of the ATPases tested in vivo: only the activity of Ca(+2)-ATPase decreased whereas that of Mg(+2)-ATPase increased significantly. In vitro experiments, prior incubation of isolated synaptosomes with glucose of concentrations corresponding to normoglycemia in vivo (4.5 - 6.5 mM), stimulated Ca(+2)-ATPase activity, whereas higher glucose concentrations (10.0 - 12.5 mM) inhibited significantly the enzyme activity. The most sensitive to hyperglycemia appeared Na(+), K(+)-ATPase in old rats synaptosomes with the progressive decline starting at 6.5 mM glucose. The activity of Mg(+2)-ATPase was not inhibited in vitro even at high glucose concentrations that may explain the increased in vivo, activity of this enzyme in old, hyperglycemic rats.