1. Dopamine β-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine β-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine β-hydroxylase, we applied a homologous human dopamine β-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine β-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine β-hydroxylase deficiency.

2. Authentic, physically stable dopamine β-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 ± 1.4 ng/ml (range: 18.5–52.5 ng/ml), but at a 283 ± 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine β-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine β-hydroxylase was suggested by incomplete correlation with plasma dopamine β-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine β-hydroxylase concentration gradient.

3. Cerebrospinal fluid dopamine β-hydroxylase was not changed by the central α2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine β-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine β-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity.

4. Cerebrospinal fluid dopamine β-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine β-hydroxylase was markedly diminished (16.3 ± 2.9 versus 31.3 ± 1.4 ng/ml, P < 0.001) and rose by 58 ± 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine β-hydroxylase deficiency, lack of detectable dopamine β-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder.

5. We conclude that cerebrospinal fluid dopamine β-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.

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