Effects of lithium chloride on parameters biosynthetic capacity for 5-hydroxytryptamin in rat brain.
Administration of lithium chloride to rats resulted in a biphasic, temporally related alteration in the brain's biosynthetic capacity for 5-hydroxytryptamine (5-HT). After 3 to 5 days of drug administration, the Vmax of the high affinity uptake of [14-C]tryptophan into striate nerve ending synaptosomes increased to 140% of control values. The stimulated uptake of radioactive precursor apparently resulted in an augmentation of tryptophan-to-5-HT conversion activity of the same magnitude in these synaptosomes. These events were succeeded by an apparently compensatory decrease in the Vmax of midbrain cell body and nerve-ending solubilized tryptophan-5-hydroxylase (EC 1.99.1.4). After 21 days of drug administration, [14-C]tryptophan uptake remained above control levels, but striate synaptosomal conversion activity had returned to control levels. In contrast, soluble midbrain and solubilized striate synaptosomal enzyme activity remained significantly below control values. In vitro lithium chloride at 10 or 53 mM had no effect on soluble tryptophan hydroxylase activity, but either concentration of lithium chloride significantly enhanced the uptake of [14-C]tryptophan into striate synaptosomes, and consequently also the synaptosomal conversion of tryptophan to 5-HT. Increasing tryptophan levels either by preincubation of synaptosomes with L-tryptophan or by administration of L-tryptophan loads (20-60 mg/kg) resulted in augmented [14-C]tryptophan uptake and conversion activity. The sequence of events that we observed after lithium treatment is consistent with receptor-mediated neuronal feedback regulation of tryptophan hydroxylase activity after stimulation of tryptophan uptake and conversion of 5-HT.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005246:Feedback; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis* / Q000378:metabolism; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D012701:Serotonin; D014443:Tyrosine; D014364:Tryptophan; D008094:Lithium; D014365:Tryptophan Hydroxylase