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 no repinephrine. The significance of plasma DOPA has not been elucidated. One would expect that substantial amounts of DOPA are derived from sy mpathetic nerves. There appears, however, neither to be a depot of DOP A in nerves nor is there a close correlation between plasma DOPA and s ympathetic activity. The aim of the present study was to obtain furthe r information about plasma DOPA by studying DOPA kinetics in healthy h umans both with and without inhibition of DOPA decarboxylase by benser azide. Plasma DOPA and other catecholamines were measured by reverse-p hase HPLC with electrochemical detection and DOPA clearance and appear ance rate were studied using infusion of H-3-DOPA. The plasma clearanc e 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 mu g min(-1) and the extr emities accounted for approximately 1/5 of this value. After inhibitio n of DOPA decarboxylase by benserazide the DOPA appearance rate increa sed 7-fold, whereas the DOPA clearance only decreased slightly and ins ignificantly. These findings are probably explained by two factors: (1 ) There is normally a large production of DOPA in some tissues from wh ich DOPA spillover into plasma only occurs to a minor extent and trace r DOPA only mixes with this compartment to a small degree; (2) These c ompartments are permeable to benserazide, which blocks the decarboxyla tion of DOPA, which then leaves the tissues and spillover to plasma. O ur results are compatible with the view that substantial amounts of DO PA are normally decarboxylated in sympathetic nerves, and spillover to plasma only if DOPA cannot be decarboxylated to dopamine. We conclude that plasma DOPA concentration neither reflects sympathetic nerve act ivity nor tyrosine hydroxylase activity. Provided plasma DOPA to a maj or extent is derived from sympathetic nerves it probably reflects the minimal fraction of DOPA synthesized but not decarboxylated to dopamin e in nerves.