Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis.
Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase. NSD-1015 increased the concentration of L-DOPA much higher than that of 5-HTP in a dose-related manner (1-100 mumol/L). In order to examine the relationship between dopaminergic and serotonergic neurons in the striatum, either 5-HTP or L-DOPA was injected intraperitoneally to rats pretreated with benserazide, an inhibitor of peripheral decarboxylase. 5-HTP administration increased 5-HTP, but decreased L-DOPA in a dose-dependent manner. Conversely, 5-HTP concentration decreased in an association with the increased content of L-DOPA following L-DOPA administration. The decrease of 5-HTP caused by L-DOPA administration was not as remarkable as that of L-DOPA by 5-HTP injection. These results suggest that L-DOPA and 5-HTP, the precursor amino acids for catecholamines and indoleamines, could affect mutually each other neuronal activity through the inhibition of their rate-limiting enzymes.
Hashiguti
H
H
Department of Psychiatry, Miyazaki Medical College, Japan.
Nakahara
D
D
Maruyama
W
W
Naoi
M
M
Ikeda
T
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D006719:Homovanillic Acid / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006900:Hydroxylation; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D014443:Tyrosine; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D004298:Dopamine; D006719:Homovanillic Acid