Effects of L-DOPA/carbidopa administration on the levels of L-DOPA, other amino acids and related compounds in the plasma, brain and heart of the rat.
Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brainstem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < or = 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, camosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson's disease.
Diederich
C
C
Department of Pharmacology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Milakofsky
L
L
Hare
T A
TA
Hofford
J M
JM
Dadmarz
M
M
Vogel
W H
WH
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000097:blood / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D007980:Levodopa; D002230:Carbidopa