Tryptophan hydroxylase: increase in activity by electrical stimulation of serotonergic neurons

Electrical stimulation of the rat midbrain dorsal raphe nucleus, which contains clusters of 5-HT containing cell bodies, increased the activity of tryptophan hydroxylase prepared in low speed supernatant extracts from cerebral cortex, a region containing 5-HT projections arising from the dorsal raphe nucleus. In contrast, activity of enzyme from hippocampus, which receives its 5-HT innervation primarily from the median raphe was unaffected by dorsal raphe stimulation. The activity of cortical enzyme increased maximally at a stimulation frequency between 10 and 15 Hz. The increase in activity took 20 min to reach maximum at a stimulation frequency of 10 Hz and had returned to control levels 30 min after cessation of stimulation. The increase in enzyme activity is associated with a significant increase in V(max) without any change in K(m) for substrate tryptophan or the artificial reduced pterin cofactor, d-6-methyl-5,6,7,8-tetrahydropterin. These findings may provide a basis for the increase in synthesis of 5-HT which occurs in response to nerve stimulation through the enhanced conversion of tryptophan to 5-hydroxytryptophan.