DOPAMINE-BETA-HYDROXYLASE IMMUNOREACTIVITY IN HUMAN CEREBROSPINAL-FLUID - PROPERTIES, RELATIONSHIP TO CENTRAL NORADRENERGIC NEURONAL-ACTIVITY AND VARIATION IN PARKINSONS-DISEASE AND CONGENITAL DOPAMINE-BETA-HYDROXYLASE DEFICIENCY

1. Dopamine beta-hydroxylase is stored and released with catecholamine s by exocytosis from secretory vesicles in noradrenergic neurons and c hromaffin cells. Although dopamine beta-hydroxylase enzymic activity i s measurable in cerebrospinal fluid, such activity is unstable, and it s relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopami ne beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid do pamine beta-hydroxylase, as well as its relationship to central noradr energic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta -hydroxylase deficiency. 2. Authentic, physically stable dopamine beta -hydroxylase immunoreactivity was present in normal human cerebrospina l 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 plasm a. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrat ions were correlated (r=0.67, P=0.001). Some degree of local central n ervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hyd roxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-h ydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine bet a-hydroxylase was not changed by the central alpha(2)-agonist clonidin e at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subj ects to cerebrospinal fluid concentrations of noradrenaline or methoxy hydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxyla se concentration was not closely linked either pharmacologically or bi ochemically to central noradrenergic neuronal activity. 4. Cerebrospin al fluid dopamine beta-hydroxylase was not changed in essential hypert ension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydr oxy)ase 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 chromaf fin cell autografts. In congenital dopamine beta-hydroxylase deficienc y, lack of detectable dopamine beta-hydroxylase immunoreactivity in ce rebrospinal fluid or plasma suggests absent enzyme (rather than a cata lytically defective enzyme) as the origin of the disorder. 5. We concl ude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivit y, while not closely linked to central noradrenergic neuronal activity , is at least in part derived from the central nervous system, and tha t its measurement may be useful in both the diagnosis and treatment of neurological disease.