Glycogen phosphorylase activity in the cerebral cortex of rats during development: effect of homocysteine-induced seizures.

The aim of the present study was to examine the total, as well as the active form of glycogen phosphorylase in the rat cerebral cortex during development, and to assess the response of the enzyme to induced seizures. Seizures were induced in 7-, 12- and 18-day-old male Wistar rats by i.p. administration of DL-homocysteine thiolactone HCl. Total glycogen phosphorylase activity increased from 54.76 + 2.33 to 181.14 +/- 5.79 micromol/g/h and phosphorylase a from 3.45 +/- 0.45 to 63.73 +/- 1.41 micromol/g/h, from postnatal day 7 to 18, respectively. In 7-day-old pups phosphorylase a corresponded to only 6% of total activity. At the onset of seizures a marked rise (34-90%) in active phosphorylase occurred in all age groups. Thus, in the brains of immature animals a rapid conversion of phosphorylase b to a can occur in response to increased cellular activity. However, in 7-day-old rats, in spite of marked activation, phosphorylase a remained very low (6.0 +/- 0.42 micromol/g/h) and can thus explain the slow onset of glycogenolysis in this age group. Cyclic AMP levels remained unchanged at the onset of seizures in 7- and 12-day-old pups, and only a mild (+ 25%) rise was observed in 18-day-old rats. The marked increase of phosphorylase a in 7- and 12-day-old rats thus occurred in the presence of unchanged levels of cAMP, suggesting the involvement of cAMP-independent mechanism of activation, in which Ca2+ most probably plays a role.