Neuronal source of plasma dopamine.
BACKGROUND
Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested in humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves.


METHODS
We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomies (SNS-x), or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not.


RESULTS
Orthostasis, YOH, ISO, and TYR increased and TRI/PEN decreased plasma DA concentrations. Individual values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%-4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%-90% of plasma DA has a sympathoneural source.


CONCLUSIONS
Plasma DA is derived substantially from sympathetic noradrenergic nerves.
Goldstein
David S
DS
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
Holmes
Courtney
C
D016022:Case-Control Studies; D004244:Dizziness; D004298:Dopamine / Q000097:blood*; D005089:Exocytosis; D005934:Glucagon / Q000008:administration & dosage; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D019636:Neurodegenerative Diseases / Q000097:blood; D009474:Neurons / Q000378:metabolism*; D015016:Yohimbine / Q000008:administration & dosage
D015016:Yohimbine; D005934:Glucagon; D007545:Isoproterenol; D004298:Dopamine
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