Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1991;16(11):1199–1205. doi: 10.1007/BF00966696

Accumulation of noradrenaline and its oxidation products by cultured rodent astrocytes

John X Wilson 1, Greame A R Wilson 1
PMCID: PMC7089007  PMID: 1815135

Abstract

The accumulation of [3H]noradrenaline ([3H]NA) and its oxidation products was studied in primary cultures of cerebral astrocytes. Astroglial accumulation of radiolabeled catecholamine ([3H] NA and oxidation products) was enhanced by manganese or iron, but it was inhibited by unlabeled NA, dopamine or ascorbate. Tissue:medium ratios of radioactivity increased as extracellular [3H]NA was oxidized. When extracellular oxidation was prevented by ascorbate, as confirmed by high performance liquid chromatography with electrochemical detection, either ouabain pretreatment or nominally Na+-free incubation medium inhibited approximately one-half of specific [3H]NA accumulation by rat (but not mouse) astrocytes. These observations suggest that neurological responses to trace metals and ascorbate may arise from the effects of these agents on the clearance of extracellular catecholamines. Astrocytes can accumulate oxidation products of NA more rapidly than they take up NA itself, but ascorbate at physiological concentrations prevents the oxidation process in extracellular fluid. Furthermore, in the presence of ascorbate, Na+-dependent transport mediates a significant component of NA accumulation in rat astrocytes.

Key Words: Catecholamine transport, catecholamine oxidation, ascorbate, astrocytes, rat brain, mouse brain

References

  • 1.Kimelberg H. K., Pelton E. W. High affinity uptake of [3H]norepinephrine by primary astrocyte cultures and its inhibition by tricyclic antidepressants. J. Neurochem. 1983;40:1265–1270. doi: 10.1111/j.1471-4159.1983.tb13565.x. [DOI] [PubMed] [Google Scholar]
  • 2.Semenoff D., Kimelberg H. K. Autoradiography of high affinity uptake of catecholamines by primary astrocyte cultures. Brain Res. 1985;348:125–136. doi: 10.1016/0006-8993(85)90368-3. [DOI] [PubMed] [Google Scholar]
  • 3.Kimelberg H. K., Katz D. M. Regional differences in 5-hydroxytryptamine and catecholamine uptake in primary astrocyte cultures. J. Neurochem. 1986;47:1647–1652. doi: 10.1111/j.1471-4159.1986.tb00808.x. [DOI] [PubMed] [Google Scholar]
  • 4.Kimelberg H. K., Goderie S. K. Effect of ascorbate on Na+-independent and Na+-dependent uptake of [3H]norepinephrine in primary astrocyte cultures. Trans. Am Soc. Neurochem. 1991;22:102. [Google Scholar]
  • 5.Hansson E. Astroglia from defined brain regions as studied with primary cultures. Prog. Neurobiol. 1988;30:369–397. doi: 10.1016/0301-0082(88)90008-1. [DOI] [PubMed] [Google Scholar]
  • 6.Paterson I. A., Hertz L. Na+ independent transport of noradrenaline in mouse and rat astrocytes in culture. J. Neurosci. Res. 1989;23:71–77. doi: 10.1002/jnr.490230110. [DOI] [PubMed] [Google Scholar]
  • 7.Das K. C., Abramson M. B., Katzman R. A new chemical method for quantifying melanin. J. Neurochem. 1976;26:695–699. doi: 10.1111/j.1471-4159.1976.tb04439.x. [DOI] [PubMed] [Google Scholar]
  • 8.Graham D. G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytoxic quinones. Mol. Pharmacol. 1978;14:633–643. [PubMed] [Google Scholar]
  • 9.Graham D. G. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease. Neurotoxicology. 1984;5:83–96. [PubMed] [Google Scholar]
  • 10.Borit A., Rubinstein L. J., Urich H. The striatonigral degenerations. Putaminal pigments and nosology. Brain. 1975;98:101–112. doi: 10.1093/brain/98.1.101. [DOI] [PubMed] [Google Scholar]
  • 11.Friede R. L. Striato-nigral astrocytic melanization. J. Neurol. 1979;220:149–156. doi: 10.1007/BF00705533. [DOI] [PubMed] [Google Scholar]
  • 12.Juurlink B. H. J. Lysosomal accumulation of neuromelanin-like material in astrocytes after exposure to norepinephrine. J. Neuropathol. Exp. Neurol. 1988;47:48–53. doi: 10.1097/00005072-198801000-00006. [DOI] [PubMed] [Google Scholar]
  • 13.Oh C., Gardiner T. W., Rebec G. V. Blockade of both D1- and D2-dopamine receptors inhibits amphetamine-induced ascorbate release in the neostriatum. Brain Res. 1989;480:184–189. doi: 10.1016/0006-8993(89)91581-3. [DOI] [PubMed] [Google Scholar]
  • 14.Tolbert L. C., Thomas T. N., Middaugh L. D., Zemp J. W. Effect of ascorbic acid on neurochemical, behavioral, and physiological systems mediated by catecholamines. Life Sci. 1979;25:2189–2195. doi: 10.1016/0024-3205(79)90091-2. [DOI] [PubMed] [Google Scholar]
  • 15.Wagner G. C., Carelli R. M., Jarvis M. F. Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats. Res. Comm. Chem. Path. Pharmacol. 1985;47:221–228. [PubMed] [Google Scholar]
  • 16.Dorris R. L., Dill R. E. Potentiation of haloperidol-induced catalepsy by ascorbic acid in rats and nonhuman primates. Pharmacol. Biochem. Behav. 1986;24:781–783. doi: 10.1016/0091-3057(86)90592-7. [DOI] [PubMed] [Google Scholar]
  • 17.Wilson J. X. Ascorbic acid regulates norepinephrine uptake by cultured cerebral astrocytes. Proc. Can. Fed. Biol. Soc. 1987;30:134. [Google Scholar]
  • 18.Wilson J. X. Uptake of norepinephrine and its oxidation products by cerebral glial cells. Am. Zool. 1987;27:129A. [Google Scholar]
  • 19.Wilson J. X., Walz W. Catecholamine uptake into cultured mouse astrocytes. In: Boulton A. A., Juorio A. V., Downer R. G. R., editors. Trace Amines; Comparative and Clinical Neurobiology. Clifton, U.S.A.: Human Press; 1988. pp. 301–305. [Google Scholar]
  • 20.Izquierdo J. A., Jofre I. J., Acevedo C. The effect of ascorbic acid on the cerebral and adrenal catecholamine content in the male rat. J. Pharm. Pharmac. 1968;20:210–214. doi: 10.1111/j.2042-7158.1968.tb09723.x. [DOI] [PubMed] [Google Scholar]
  • 21.Saner A., Weiser H., Hornig D., Da Prada M., Pletscher A. Cerebral monoamine metabolism in guinea pigs with ascorbic acid deficiency. J. Pharm. Pharmac. 1975;27:896–902. doi: 10.1111/j.2042-7158.1975.tb10244.x. [DOI] [PubMed] [Google Scholar]
  • 22.Hertz L., Juurlink B. H. J., Fosmark H., Schousboe A. Methodological appendix: Astrocytes in primary cultures. In: Pfeiffer S. E., editor. Neuroscience Approached Through Cell Culture, Vol. 1. Boca Raton, Florida: CRC Press; 1982. pp. 175–186. [Google Scholar]
  • 23.Rothfels K. H., Axelrad A. A., Siminovitch L., McCulloch E. A., Parker R. C. The origin of altered cell lines from mouse, monkey and man as indicated by chromosome and transplantation studies. Can. Cancer. Conf. 1959;3:189–214. [Google Scholar]
  • 24.Wilson G. A. R., Beushausen S., Dales S. In vivo and in vitro models of demyelinating diseases: XV. Differentiation influences on the regulation of coronavirus infection in primary explants of mouse CNS. Virology. 1986;151:253–264. doi: 10.1016/0042-6822(86)90047-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Hertz L., Juurlink B. H. P., Szuchet S. Cell cultures. In: Lajtha A., editor. Handbook of Neurochemistry. 2nd Edition. New York: Plenum Press; 1985. pp. 603–661. [Google Scholar]
  • 26.Naus C. C. G., Bechberger J. F., Caveney S., Wilson J. X. Expression of gap junction genes in astrocytes and C6 glioma cells. Neurosci. Lett. 1991;126:33–36. doi: 10.1016/0304-3940(91)90364-y. [DOI] [PubMed] [Google Scholar]
  • 27.Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. Protein measurement with the folin phenol reagent. J. Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 28.Pasantes-Morales H., Schousboe A. Release of taurine from astrocytes during potassium-evoked swelling. Glia. 1989;2:45–50. doi: 10.1002/glia.440020105. [DOI] [PubMed] [Google Scholar]
  • 29.Pileblad E., Slivka A., Bratvold D., Cohen G. Studies on the autoxidation of dopamine: interaction with ascorbate. Arch. Biochem. Biophys. 1988;263:447–452. doi: 10.1016/0003-9861(88)90657-1. [DOI] [PubMed] [Google Scholar]
  • 30.Donaldson J., LaBella F. S., Gesser D. Enhanced autoxidation of dopamine as a possible basis of manganese neurotoxicity. Neurotoxicology. 1980;2:53–64. [PubMed] [Google Scholar]
  • 31.Riederer P., Sofic E., Rausch W.-D., Schmidt B., Reynolds G. P., Jellinger K., Youdim M. B. H. Transition metals, ferritin, glutathione, and ascorbic acid in Parkinsonian brains. J. Neurochem. 1989;52:515–520. doi: 10.1111/j.1471-4159.1989.tb09150.x. [DOI] [PubMed] [Google Scholar]
  • 32.Chandra S. V., Shukla G. S. Concentrations of striatal catecholamines in rats given manganese chloride through drinking water. J. Neurochem. 1981;36:683–687. doi: 10.1111/j.1471-4159.1981.tb01642.x. [DOI] [PubMed] [Google Scholar]
  • 33.Autissier N., Rochette L., Dumas P., Beley A., Loireau A., Bralet J. Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration. Toxicology. 1982;24:175–182. doi: 10.1016/0300-483x(82)90055-5. [DOI] [PubMed] [Google Scholar]
  • 34.Deskin R., Bursian S. J., Edens F. W. Neurochemical alterations induced by manganese chloride in neonatal rats. Neurotoxicology. 1980;2:65–73. [PubMed] [Google Scholar]
  • 35.Seth P. K., Chandra S. V. Neurotransmitters and neurotransmitter receptors in developing and adult rats during manganese poisoning. Neurotoxicology. 1984;5:67–76. [PubMed] [Google Scholar]
  • 36.Kontur P. J., Fechter L. D. Brain regional manganese levels and monoamine metabolism in manganese-treated neonatal rats. Neurotox. Teratol. 1988;10:295–303. doi: 10.1016/0892-0362(88)90031-1. [DOI] [PubMed] [Google Scholar]
  • 37.Bien E., Skorka G., Rex H., Kastner D. Cerebral levels of ascorbic acid in developing rats. Biogenic Amines. 1988;5:551–555. [Google Scholar]
  • 38.Heikkila R. E., Manzino L. Ascorbic acid, redox cycling, lipid peroxidation, and the binding of dopamine receptor antagonists. Ann. N.Y. Acad. Sci. 1987;496:63–76. doi: 10.1111/j.1749-6632.1987.tb23751.x. [DOI] [PubMed] [Google Scholar]
  • 39.Rosenberg P. A. Catecholamine toxicity in cerebral cortex in dissociated cell culture. J. Neurosci. 1988;6:2887–2894. doi: 10.1523/JNEUROSCI.08-08-02887.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Lai J. C. K., Lim L., Davison A. N. Effects of Cd2+, Mn2+, and Al3+ on rat brain synaptosomal uptake of noradrenaline and serotonin. J. Inorgan. Biochem. 1982;17:215–225. doi: 10.1016/s0162-0134(00)80100-2. [DOI] [PubMed] [Google Scholar]
  • 41.Wilson J. X., Dixon S. J. Ascorbic acid transport in mouse and rat astrocytes is reversibly inhibited by furosemide, SITS, and DIDS. Neurochem. Res. 1989;14:1169–1175. doi: 10.1007/BF00965504. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neurochemical Research are provided here courtesy of Nature Publishing Group

RESOURCES