Increased tryptophan hydroxylase activity in serotonergic nerve terminals spared by 5,7-dihydroxytryptamine.
Adult rats received intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) to destroy serotonin (5-HT)-containing nerve terminals throughout the brain. When the animals were killed 3 or 21 days later, we observed a marked decrease in 5-HT content in septum and hippocampus and a parallel decline in in vitro high affinity 5-HT uptake. 5-Hydroxyindoleacetic acid (5-HIAA) concentrations also were reduced but by a much smaller extent, resulting in significant increases in the ratio of 5-HIAA to 5-HT. These changes were accompanied by similar increases in the ratio of tryptophan hydroxylase (TPH) activity to 5-HT content. The relative increases in TPH activity resulted from two temporally distinct processes, the first of which appeared to be an activation that could be mimicked in vitro by Ca2+-dependent phosphorylation. We conclude that, after partial damage to 5-HT neurons, there is a compensatory increase in the synthesis and release of 5-HT from those terminals that remain.
Stachowiak
M K
MK
Stricker
E M
EM
Jacoby
J H
JH
Zigmond
M J
MJ
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D005246:Feedback; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011903:Raphe Nuclei / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000032:analysis*
D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase