Summary
The concentration of free and conjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) were measured by a modified radioenzymatic assay in the plasma and in the cerebrospinal fluid (CSF) of 45 patients with normal and in 21 patients with disturbed blood-CSF barriers. In patients with an undisturbed blood-CSF barrier the free NE and E in CSF were 128±45 ng/l and 27±20 ng/l (mean values±S.E.), respectively, and represented about 50 % of the average plasma values. Mean DA was not different in plasma (47±22 ng/l) and in CSF (41±19 ng/l). Both in plasma and in CSF, considerable higher free catecholamine (CA) levels were measured in patients with dysfunction of the blood-CSF barrier. In one patient with bacterial meningitis twofold higher concentrations of free NE and DA in CSF as compared with plasma were detectable. Sulfate conjugates of catecholamines are predominant in plasma and CSF.
The contribution of conjugated CA to total CA in plasma from patients with normal blood-CSF barrier averaged 69.7 %, 63.1 % and 98.1 % for NE, E and DA, respectively and was significantly lower in the CSF (p<0.001). In patients with disturbed blood-CSF barrier, the increases of conjugated CA were more pronounced in CSF than in plasma. Further, the contribution of conjugated NE and E to total NE and E in CSF was not only increased in patients with bacterial meningitis, but also in patients with renal insufficiency compared to the “control” patients (p<0.02 and p<0.001 resp.). Free and conjugated NE, E and DA in the plasma and CSF were related significantly (p<0.01 resp.) with stronger correlation for conjugated CA (p<0.001 resp.). These results together with findings in the literature, suggest that there is little or no rostral-caudal gradient in CSF CA conjugate concentrations and that even in patients with intact blood-CSF barrier plasma conjugated CA concentrations influence those in CSF. Thus only free CA levels in CSF may reflect the central adrenergic activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson, R. J., Weinshilboum, R. M.: Phenolsulfotransferase in human tissue. Radiochemical enzymatic assay and biochemical properties. Clin. Chim. Acta103, 79–80 (1980).
Buu, N. T., Duhaime, J., Kuchel, O., Genest, J.: The convulsive effects of dopamine sulfate conjugates in rat brain. Life Sci.29, 2311–2316 (1981).
Bosak, J., Knoll, E., Ratge, D., Wisser, H.: Single-isotope enzymatic derivative method for measuring catecholamines in human plasma. J. Clin. Chem. Clin. Biochem. 18, 413–421 (1980).
Claustre, J., Serusclat, P., Peyrin, L.: Glucuronide and sulfate catecholamine conjugates in rat and human plasma. J. Neural Transmission56, 265–278 (1983).
Dencker, S. J., HÄggendal, J., Ilves-HÄggendal, M.: Presence of free and conjugated noradrenaline in human cerebrospinal fluid. Acta Physiol. Scand.69, 140–146 (1967).
Jenner, W. M., Rose, F. A.: Studies on the sulphation of 3, 4-dihydroxyphenyl-ethlamine (dopamine) and related compounds by rat tissues. Biochem. J.135, 109–114 (1973).
Johnson, G. A., Baker, C. A., Smith, R. T.: Radioenzymatic assay of sulfate conjugates of catecholamines and dopa in plasma. Life Sci.26, 1591–1598 (1980).
Karoum, F.: Presence, distribution and pharmacology of conjugated catecholamines in the rat spinal cord. Brain Res.259, 251–266 (1983).
Klensch, H., Gött, U.: Liquor-Adrenalin und -Noradrenalin im Operationsstress. Klin. Wschr.48, 853–855 (1970).
Kuchel, O., Buu, N. T., Hamet, P., Larochelle, P., Bourque, M., Genest, J.: Essential hypertension with low conjugated catecholamines imitates pheochromocytoma. Hypertension3, 347–351 (1981).
Lake, C. R., Ziegler, M. G., Kopin, I. J.: Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life Sci.18, 1315–1326 (1976).
Manshardt, J., Wurtmann, R. J.: Daily rhythm in the noradrenaline content of rat hypothalamus. Nature (London)217, 574–575 (1968).
Meyer, J. S., Stoica, E., Parscu, I., Shimazu, K., Hartmann, A.: Catecholamine concentrations in CSF and plasma of patients with cerebral infarction and hemorrhage. Brain96, 277–288 (1973).
Peuler, J. D., Johnson, G. A.: Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci.21, 625–636 (1977).
Ratge, D., Knoll, E., Diener, U., Hadjidimos, A., Wisser, H.: Altered circadian rhythm of catecholamines in patients with apallic syndrome. Experientia37, 1207–1209 (1981).
Ratge, D., Baumgardt, G., Knoll, E., Wisser, H.: Plasma free and conjugated catecholamines in diagnosis and localisation of pheochromocytoma. Clin. Chim. Acta132, 229–243 (1983).
Reiber, H.: The discrimination between different blood-CSF barrier dysfunctions and inflammatory reactions of the CNS by a recent evaluation graph for the protein profile of cerebrospinal fluid. J. Neurol.224, 89–99 (1980).
Renskers, K. J., Feor, K. D., Roth, J. A.: Sulfation of dopamine and other biogenic amines by human brain phenolsulfotransferase. J. Neurochem.34, 1362–1368 (1980).
Reis, D. J., Wurtmann, R. J.: Diurnal changes in brain noradrenaline. Life Sci.7, 91–98 (1968).
Roth, J. A., Rivett, A. J.: Does sulfate conjugation contribute to the metabolic inactivation of catecholamines in humans? Biochem. Pharmac.31, 3017–3021 (1982).
Sato, S., Suziki, T.: Anatomical mapping of the cerebral neovi vasorum in the human brain. J. Neurosurg.43, 559–568 (1975).
Scheinin, M., Seppala, T., Koulo, M., Linnoila, M.: Determination of conjugated dopamine in cerebrospinal fluid from humans and non-humans primates with high performance liquid chromatography using electrochemical detection. Acta pharmacol. et toxicol.55, 88–94 (1984).
Sharpless, N. S., Tyce, G. M., Thal, L. J., Waltz, J. M., Tabaddor, K., Wolfxon, L. I.: Free and conjugated dopamine in human ventricular fluid. Brain Res.217, 107–118 (1981).
Sinha, J. N., Deitl, H., Philippu, A.: Effect of a fall of blood pressure on the release of catecholamines in the hypothalamus. Life Sci.26, 1751–1760 (1980).
Tyce, G. M., Sharpless, N. S., Kerr, F. W., Muenter, M. D.: Dopamine conjugate in cerebrospinal fluid. J. Neurochem.34, 210–212 (1980).
Wang, P.-C., Buu, N. T., Kuchel, O., Genest, J.: Conjugation patterns of endogenous plasma catecholamines in human and rat. J. Lab. Clin. Med.101, 141–151 (1983).
Weil-Malherbe, H., Axelrod, J., Tomchick, R.: Blood-brain barrier for adrenaline. Science129, 1226–1227 (1959).
Ziegler, M. G., Lake, C. R., Kopin, I. J.: Norepinephrine in cerebrospinal fluid. Brain Res.108, 436–440 (1976a).
Ziegler, M. G., Lake, C. R., Wood, J. H., Brooks, B. R., Ebert, M. H.: Relationship between norepinephrine in blood and cerebrospinal fluid in the presence of a blood-cerebrospinal fluid barrier for norepinephrine. J. Neurochem.28, 677–679 (1976b).
Ziegler, M. G., Lake, C. R., Wood, J. H., Ebert, M. H.: Circadian rhythm in cerebrospinal noradrenaline of man and monkey. Nature264, 656–658 (1976c).
Ziegler, M. G., Lake, C. R., Wood, J. H., Brooks, B. R.: Relationship between cerebrospinal fluid norepinephrine and blood pressure in neurologic patients. Clin. Exp. Hypertension2, 995–1008 (1980a).
Ziegler, M. G., Lake, C. R., Wood, J. H., Ebert, M. H.: Norepinephrine in cerebrospinal fluid: basic studies, effects of drugs and disease. In: Neurobiology of the Cerebrospinal Fluid (Wood, J. H., ed.), Vol. 1, pp. 141–149. New York: Plenum Press. 1980b.
Zivin, J. A., Raid, J. L., Saaverda, J. M., Kopin, I. J.: Quantitative localization of biogenic amines in spinal cord. Brain Res.99, 293–301 (1975).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ratge, D., Bauersfeld, W. & Wisser, H. The relationship of free and conjugated catecholamines in plasma and cerebrospinal fluid in cerebral and meningeal disease. J. Neural Transmission 62, 267–284 (1985). https://doi.org/10.1007/BF01252241
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01252241