Increase in plasma 3,4-dihydroxyphenylalanine (DOPA) appearance rate after inhibition of DOPA decarboxylase in humans.
Concentrations of DOPA in plasma are relatively high as compared to norepinephrine. The significance of plasma DOPA has not been elucidated. One would expect that substantial amounts of DOPA are derived from sympathetic nerves. There appears, however, neither to be a depot of DOPA in nerves nor is there a close correlation between plasma DOPA and sympathetic activity. The aim of the present study was to obtain further information about plasma DOPA by studying DOPA kinetics in healthy humans both with and without inhibition of DOPA decarboxylase by benserazide. Plasma DOPA and other catecholamines were measured by reverse-phase HPLC with electrochemical detection and DOPA clearance and appearance rate were studied using infusion of 3H-DOPA. The plasma clearance of DOPA was 1.02 1 min-1. Approximately 20% of this value could be explained by DOPA being decarboxylated in the kidneys and excreted as dopamine. The DOPA appearance rate was 1.13 micrograms min-1 and the extremities accounted for approximately 1/5 of this value. After inhibition of DOPA decarboxylase by benserazide the DOPA appearance rate increased 7-fold, whereas the DOPA clearance only decreased slightly and insignificantly. These findings are probably explained by two factors: (1) There is normally a large production of DOPA in some tissues from which DOPA spillover into plasma only occurs to a minor extent and tracer DOPA only mixes with this compartments to a small degree; (2) These compartments are permeable to benserazide, which blocks the decarboxylation of DOPA, which then leaves the tissues and spillover to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Eldrup
E
E
Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen, Denmark.
Hetland
M L
ML
Christensen
N J
NJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood; D000328:Adult; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000097:blood* / Q000493:pharmacokinetics; D004298:Dopamine / Q000097:blood; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D001545:Benserazide; D004298:Dopamine