Plasma dihydroxyphenylalanine and total body and regional noradrenergic activity in humans

Abstract

Dihydroxyphenylalanine (DOPA) is the immediate product of the rate-limiting step in catecholamine biosynthesis, hydroxylation of tyrosine. This study examined whether plasma concentrations of DOPA are related to tyrosine hydroxylase activity. Plasma concentrations of DOPA, norepinephrine, and the norepinephrine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in arterial blood and blood draining the heart, brain, and forearm of 21 patients undergoing cardiac catheterization. Rates of entry of norepinephrine into arterial plasma and plasma draining the heart were estimated using infusions of radioactive norepinephrine. Arterial plasma DOPA correlated positively with arterial plasma DHPG (r = 0.63), MHPG (r = 0.47), norepinephrine (r = 0.67), and the rate of entry of norepinephrine into arterial plasma (r = 0.62). There were significant arteriovenous increments in plasma DOPA: 28% across the heart, 18% across the brain, and 32% across the forearm. Arteriovenous increments in plasma DOPA across the brain correlated positively with increments in plasma DHPG (r = 0.83), but not with increments in norepinephrine or MHPG. In the arm, where MHPG was the major metabolite, arteriovenous increments in DOPA correlated positively with increments in MHPG (r = 0.52) and with the combined increments in MHPG, DHPG, and norepinephrine (r = 0.60). In the heart, where DHPG was the major metabolite, arteriovenous increments in DOPA correlated positively with increments in DHPG (r = 0.72) and the combined increments in DHPG, MHPG, and norepinephrine (r = 0.62). The rate at which norepinephrine entered the great cardiac venous plasma from tissues of the heart correlated positively with the rate at which DOPA overflowed from the heart into the systemic circulation (r = 0.56). The relationships between plasma DOPA and norepinephrine metabolism and the rates of norepinephrine entry into plasma support the view that plasma DOPA reflects tyrosine hydroxylase activity.