Abstract
The plasma concentrations of noradrenaline (NA) and its primary neuronal metabolite, dihydroxyphenylglycol (DOPEG), were examined during graded orthostasis and NA infusion in 13 healthy subjects to estimate the NA concentration difference between the site of neuronal DOPEG formation and that in plasma.
Stimulation of NA release by graded orthostasis resulted in similar absolute increments in plasma NA and DOPEG with both plasma concentrations being dependent on the degree of orthostasis. The mean value of the ΔDOPEG/ΔNA ratio amounted to 0.999 (0.745; 1.341). NA was infused i.v. during two consecutive 30-min periods at constant rates of 0.43 and 0.86 nmol kg−1 min−1, respectively. This infusion resulted in a ΔDOPEG/ΔNA ratio of 0.048 (0.036; 0.064) for the first and 0.078 (0.067; 0.090) for the second infusion period (p < 0.01).
For each individual subject, the factor quantifying the NA concentration difference between the site of neuronal DOPEG formation and plasma was calculated from the square root of the ratio of ‘ΔDOPEG/ΔNA during orthostasis to ΔDOPEG/ΔNA during the low rate of NA infusion’. The average NA concentration at the site of neuronal DOPEG formation (i.e. the axoplasm of noradrenergic neurones) was found to be 4.6-fold higher than that in plasma.
Similar content being viewed by others
References
Langer SZ, Farah MB, Luchelli-Fortis MA, Adler-Graschinsky E, Filinger EJ. Metabolism of endogenous noradrenaline. In: Tuomisto J, Paasonen MK, eds.Proceedings of the 6th International Congress of Pharmacology, vol 2. Helsinki: Finnish Pharmacological Society, 1975: 17–31.
Graefe K-H, Henseling M. Neuronal and extraneuronal uptake and metabolism of catecholamines.Gen Pharmacol 1983;14: 27–33.
Kopin IJ. Catecholamine metabolism: basic aspects and clinical significance.Pharmacol Rev 1985;37: 333–346.
Graefe K-H, Bönisch H. The transport of amines across the axonal membrane of noradrenergic and dopaminergic neurones. In: Trendelenburg U, Weiner N, eds.Handbook of Exp. Pharmacol (vol 90/1). Catecholamines I. Berlin, Heidelberg, New York, London, Paris, Tokyo: Springer, 1988: 193–245.
Eisenhofer G, Goldstein DS, Ropchak TG, Nguyen HQ, Keiser HR, Kopin IJ. Source and physiological significance of plasma 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol.J Auton Nerv Syst 1988;24: 1–14.
Goldstein DS, Eisenhofer G, Stull R, Folio CJ, Keiser HR, Kopin IJ. Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans.J Clin Invest 1988;81: 213–220.
Ludwig J, Gerhardt T, Halbrügge T, Walter J, Graefe K-H. Plasma concentrations of noradrenaline and 3,4-dihydroxyphenylethyleneglycol under conditions of enhanced sympathetic activity.Eur J Clin Pharmacol 1988;35: 261–267.
Ludwig J, Halbrügge T, Vey G, Walter J, Graefe K-H. Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline.Eur J Clin Pharmacol 1989;37: 493–500.
Halbrügge T, Wölfel R, Graefe K-H. Plasma 3,4-dihydroxyphenylglycol as a tool to assess the role of neuronal uptake in the anaesthetized rabbit.Naunyn-Schmiedeberg's Arch Pharmacol 1989;340: 726–732.
Ludwig J, Gerlich M, Halbrügge T, Graefe K-H. The synaptic noradrenaline concentration in humans as estimated from simultaneous measurements of plasma noradrenaline and dihydroxyphenylglycol (DOPEG).J Neural Transm 1990;32 (suppl): 441–445.
Halbrügge T, Gerhardt T, Ludwig J, Heidbreder E, Graefe K-H. Assay of catecholamines and dihydroxyphenylethyleneglycol in human plasma and its application in orthostasis and mental stress.Life Sci 1988;43: 19–26.
Wallenstein S, Zucker LC, Fleiss JL. Some statistical methods useful in circulation research.Circ Res 1980;47: 1–8.
Eisenhofer G, Ropchak TG, Stull RW, Goldstein DS, Keiser HR, Kopin IJ. Dihydroxyphenylglycol and intraneuronal metabolism of endogenous and exogenous norepinephrine in the rat vas deferens.J Pharmacol Exp Ther 1987;241: 547–553.
Eisenhofer G, Esler MD, Meredith IT, Ferrier C, Lambert G, Jennings G. Neuronal re-uptake of noradrenaline by sympathetic nerves in humans.Clin Sci 1991;80: 257–263.
Esler MD, Wallin G, Dorward PK,et al. Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans.Am J Physiol 1991;260: R817-R823.
Kopin IJ, Zukowska-Grojec Z, Bayorh MA, Goldstein DS. Estimation of intrasynaptic norepinephrine concentrations at vascular neuroeffector junctionsin vivo.Naunyn-Schmiedeberg's Arch Pharmacol 1984;325: 298–305.
Goldstein DS, Zimlichman R, Stull R, Keiser HR, Kopin IJ. Estimation of intrasynaptic norepinephrine concentrations in humans.Hypertension 1986;8: 471–475.
Stute N, Trendelenburg U. The outward transport of axoplasmatic noradrenaline induced by a rise of the sodium concentration in the adrenergic nerve endings of the rat vas deferens.Naunyn-Schmiedeberg's Arch Pharmacol 1984;327: 124–132.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ludwig, J., Halbrügge, T., Gerlich, M. et al. Estimation of noradrenaline concentrations in the axoplasm of noradrenergic neurones in man. Clinical Autonomic Research 2, 159–164 (1992). https://doi.org/10.1007/BF01818956
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01818956