Assessment of dopamine and its metabolites in the intracellular and extracellular compartments of the rat striatum after peripheral administration of L-[11C]dopa.
Success in the synthesis of L-3,4-[beta-11C]dihydroxyphenylalanine (L-[11C]DOPA) and its application to positron emission tomography encouraged us to perform radioactive metabolite analyses in rats in an early phase after peripheral injection of L-[11C]DOPA. Following intravenous injection of [11C]DOPA, the radioactivity associated with DOPA and its metabolites was determined in the striatum after decapitation and in striatal extracellular fluid using in vivo brain microdialysis. Without pretreatment, 70-80% of 11C-radioactivity taken up into the striatum was associated with acidic metabolites of dopamine (DA) from 2 to 30 min after administration of L-[11C]DOPA with or without 300 micrograms/kg of unlabelled L-DOPA. In contrast, 80-90% of 11C-radioactivity in the striatum was associated with DOPA and DA after pretreatment with benserazide (25 mg/kg, i.p.) followed by administration of L-[11C]DOPA with or without unlabelled L-DOPA. The radioactivity in the DOPA fraction decreased with time (from 35% of 11C-radioactivity in the striatum at 5 min to 10% at 30 min), but that in the DA fraction increased (from 57% to 68%). The 11C-radioactivity in the extracellular fluid determined by brain microdialysis was less than 0.4% of that in the whole striatum and no radioactivity was present in the DA fraction. These results suggest that, in an early phase after administration of L-[11C]DOPA, [11C]DA is the main metabolite and is localized exclusively in the intracellular compartment within this time frame.
Miwa
S
S
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Gillberg
P G
PG
Bjurling
P
P
Yumoto
N
N
Odano
I
I
Watanabe
Y
Y
Långström
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000302:isolation & purification / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006719:Homovanillic Acid / Q000302:isolation & purification / Q000378:metabolism; D007275:Injections, Intravenous; D007424:Intracellular Fluid / Q000378:metabolism*; D007700:Kinetics; D007980:Levodopa / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism
D002250:Carbon Radioisotopes; D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D007980:Levodopa; C008404:3-methoxytyrosine; D004298:Dopamine; D006719:Homovanillic Acid