Dopaminergic transplants alter in vivo activity of tryptophan hydroxylase in the striatum in a rat model of Parkinson's disease.
L-3,4-Dihydroxyphenylalanine (L-DOPA) inhibits the activity of tryptophan hydroxylase (TRH) and thus serotonin synthesis. This inhibitory effect of L-DOPA may be related to some side effects in the patients under L-DOPA therapy. The effects of transplantation of fetal ventral mesencephalon (VM) on extracellular 5-hydroxytryptophan (5-HTP) accumulation was examined by microdialysis as an index of in vivo activity of TRH in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the rat striatum perfused with m-hydroxybenzylhydrazine (NSD-1015; an inhibitor of aromatic L-amino acid decarboxylase), L-DOPA and 5-HTP in dialysate were measured simultaneously. In response to NSD-1015, 5-HTP levels were substantially elevated in the lesion plus VM-grafted striata as compared with those in the lesion plus sham-grafted striata. The results indicate that implantation of dopamine-rich VM grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of TRH.
Ishida
Y
Y
Department of Psychiatry, Miyazaki Medical College, Japan. ishiday@post.miyazaki-med.ac.jp
Hashiguchi
H
H
Todaka
K
K
Kuwahara
I
I
Mitsuyama
Y
Y
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D016380:Brain Tissue Transplantation; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation; D007980:Levodopa / Q000494:pharmacology; D008636:Mesencephalon / Q000637:transplantation*; D017551:Microdialysis; D017072:Neostriatum / Q000201:enzymology* / Q000601:surgery; D016627:Oxidopamine / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D018663:Adrenergic Agents; D007980:Levodopa; D016627:Oxidopamine; D014365:Tryptophan Hydroxylase; D004298:Dopamine