1. To determine the sources of dopa (3,4-dihydroxyphenylalanine) in plasma, we measured regional arteriovenous differences, tissue concentrations and urinary excretion of dopa during systemic intravenous infusions of I-[3H]dopa into anaesthetized intact rats and rats pretreated with the sympathetic neurotoxin, 6-hydroxydopamine.
2. In intact rats, large arteriovenous increments in plasma dopa concentrations were noted in the femoral (47%) and adrenal (141%) beds, with a small arterial-portal venous increment (11%), whereas in the kidney there was a substantial (47%) arteriovenous decrement in plasma dopa levels. Skeletal muscle appeared to be a major source of dopa in arterial plasma.
3. Treatment with 6-hydroxydopamine abolished the afferent-efferent increment of plasma dopa concentrations in the femoral bed. The arteriovenous decrement of plasma dopa concentrations in the kidney was preserved, and the arteriovenous increment in the adrenal bed was decreased by about half. Arterial plasma dopa levels fell by 41%.
4. Regional extraction percentages of I-[3H]dopa were used to estimate the clearances and rates of appearance (spillovers) of dopa in plasma. Dopa spillover was detected in the femoral, renal, splanchnic and adrenal beds, with skeletal muscle accounting for about 44% and the kidneys accounting for about 18% of dopa in arterial plasma. Whereas chemical sympathectomy decreased the femoral and renal spillover of dopa by 90% or more, arterial dopa levels and estimated dopa spillover into arterial plasma were decreased by only about 45%.
5. The kidneys accounted for 22% of dopa clearance from arterial plasma. From the renal extraction of I-[3H]dopa and the urinary excretion of [3H]dopamine, it was estimated that 77% of dopa removed in the kidneys was excreted as dopamine in intact animals and 69% was excreted as dopamine in sympathectomized animals. Conversely, about 80% of urinary endogenous dopamine was derived from plasma dopa, regardless of 6-hydroxydopamine treatment.
6. The results indicate that endogenous dopa in arterial plasma is derived substantially but not exclusively from sympathetic nerve endings that are destroyed by 6-hydroxydopamine, especially in skeletal muscle and the kidneys. Regional dopa spillover therefore probably reflects regional catecholamine biosynthesis. In rats, urinary dopamine is derived mainly from renal decarboxylation of circulating dopa.