Activation of tyrosine hydroxylase in striatum of newborn piglets in response to hypocapnic ischemia and recovery.

The present study describes the effect of hypocapnic ischemia caused by hyperventilation on striatal levels of dopamine, DOPAC, HVA and activity of tyrosine hydroxylase in striatal synaptosomes isolated from the brain of newborn piglets. Hyperventilation did not result in statistically significant changes in the striatal level of dopamine and its major metabolites; however, it was observed that after 20 min of recovery the levels of striatal tissue dopamine, DOPAC and HVA increase by 195%, 110% and 205%, respectively. The level of DOPA (3,4-dihydroxyphenylalanine), which was used as an index of tyrosine hydroxylase activity, also increased after recovery. The rate of dopamine synthesis was 32 pmoles/mg protein/10 min in control piglets and after recovery this increased to 132 pmoles/mg protein/10 min. Measurement of the tyrosine hydroxylase activity in Triton X-100 treated synaptosomes showed that, after 20 min of recovery, there was an increase in Vmax with no change in K(m) for pteridine cofactor, compared to control. This is consistent with the enzyme having been covalently modified (activated) during tissue ischemia caused by hyperventilation and remaining activated well into the recovery period. We postulate that ischemia can induce long lasting alterations in dopamine synthesis, which may play some role in mediation of hypoxic cell injury in immature brain.