Biotransformation of locally applied L-dopa in the corpus striatum of the hemi-parkinsonian rat studied with microdialysis.
Microdialysis was used to study the biotransformation of L-dopa in intact and denervated striata of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Microdialysis probes were placed in the intact and in the denervated striatum. Observations were then made on freely moving rats. Extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) were monitored before, during and after the local administration of L-dopa via the microdialysis probe for 20 min. A dose-dependent increase in extracellular dopamine levels was seen in intact striatum after application of L-dopa in concentrations ranging between 100 nmol/l and 10 mumol/l. In the denervated striatum, the severity of the lesion influenced dopamine formation, so that no dose-effect relation could be established. The effects of the continuous intra striatal infusion of nomifensine, tetrodotoxin or benserazide on the L-dopa-induced dopamine outflow revealed that in the intact striatum this dopamine release is mainly voltage dependent. It was concluded that in the denervated striatum other cells of non-neuronal origin and containing aromatic L-amino acid decarboxylase make a major contribution to the increase in extracellular dopamine levels. Furthermore, L-dopa itself shows no dopamine-releasing properties, at least under the present experimental conditions.
Sarre
S
S
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Belgium.
De Klippel
N
N
Herregodts
P
P
Ebinger
G
G
Michotte
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001711:Biotransformation; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D013779:Tetrodotoxin; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid