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
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OCONNOR, DT
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
OCONNOR, DT
CERVENKA, JH
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
CERVENKA, JH
STONE, RA
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
STONE, RA
LEVINE, GL
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
LEVINE, GL
PARMER, RJ
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PARMER, RJ
FRANCOBOURLAND, RE
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
FRANCOBOURLAND, RE
MADRAZO, I
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MADRAZO, I
LANGLAIS, PJ
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LANGLAIS, PJ
ROBERTSON, D
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ROBERTSON, D
BIAGGIONI, I
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机构:UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
BIAGGIONI, I
机构:
[1] UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103
[2] UNIV CALIF SAN DIEGO,DEPT NEUROSCI,SAN DIEGO,CA 92103
[3] DEPT VET AFFAIRS MED CTR,SAN DIEGO,CA
[4] INST NACL NUTR SALVADOR ZUBIRAN,DEPT BIOQUIM,MEXICO CITY 14000,DF,MEXICO
[5] INST MEXICANO SEGURO SOCIAL,CTR MED SIGLO XXI,DEPT INVEST CLIN NEUROL & NEUROCIRUGIA,MEXICO CITY,DF,MEXICO
1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-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 beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-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 beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-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 beta-hydroxylase concentrations were correlated (r=0.67, P=0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha(2)-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxy)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 chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-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 beta-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.