Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Jun;83(11):4067–4070. doi: 10.1073/pnas.83.11.4067

Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation.

S I Harik
PMCID: PMC323667  PMID: 3012548

Abstract

The active transport of Na+ and K+ across the blood--brain barrier by the membrane-bound enzyme Na+/K+-activated ATPase of brain microvessel endothelial cells has a major role in the maintenance of brain water and electrolyte homeostasis. To test whether the putative noradrenergic innervation of cerebral microvessels from the nucleus locus ceruleus contributes to the regulation of Na+/K+-ATPase activity of the blood--brain barrier, specific [3H]ouabain-binding studies were performed on cerebral microvessels and crude cortical membranes obtained from Wistar rats with unilateral 6-hydroxydopamine lesion of the nucleus locus ceruleus. Such lesion depleted norepinephrine by about 90% in the ipsilateral cerebral cortex without affecting the contralateral cortex. [3H]Ouabain binding to membranes of cerebral cortex and the cerebral microvessels was specific and saturable. The maximal ouabain-binding capacity in microvessels of the ipsilateral, norepinephrine-depleted, cerebral cortex was reduced by about 40%, without change in the affinity of binding. [3H]Ouabain binding to crude membrane fractions of the cerebral cortex was not significantly affected by locus ceruleus lesion. The results suggest that Na+/K+-ATPase activity of cerebral microvessels, and the consequent transport of Na+ and K+ across the blood--brain barrier, is modulated by noradrenergic innervation from the locus ceruleus.

Full text

PDF
4067

Images in this article

4068Image
on p.4068

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akera T. Membrane adenosinetriphosphatase: a digitalis receptor? Science. 1977 Nov 11;198(4317):569–574. doi: 10.1126/science.144320. [DOI] [PubMed] [Google Scholar]
  2. Astrup J., Sørensen P. M., Sørensen H. R. Oxygen and glucose consumption related to Na+-K+ transport in canine brain. Stroke. 1981 Nov-Dec;12(6):726–730. doi: 10.1161/01.str.12.6.726. [DOI] [PubMed] [Google Scholar]
  3. Betz A. L., Firth J. A., Goldstein G. W. Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res. 1980 Jun 16;192(1):17–28. doi: 10.1016/0006-8993(80)91004-5. [DOI] [PubMed] [Google Scholar]
  4. Chaplin E. R., Free R. G., Goldstein G. W. Inhibition by steroids of the uptake of potassium by capillaries isolated from rat brain. Biochem Pharmacol. 1981 Feb 1;30(3):241–245. doi: 10.1016/0006-2952(81)90084-8. [DOI] [PubMed] [Google Scholar]
  5. Davson H. Review lecture. The blood-brain barrier. J Physiol. 1976 Feb;255(1):1–28. doi: 10.1113/jphysiol.1976.sp011267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eisenberg H. M., Suddith R. L. Cerebral vessels have the capacity to transport sodium and potassium. Science. 1979 Nov 30;206(4422):1083–1085. doi: 10.1126/science.227060. [DOI] [PubMed] [Google Scholar]
  7. Goldstein G. W. Relation of potassium transport to oxidative metabolism in isolated brain capillaries. J Physiol. 1979 Jan;286:185–195. doi: 10.1113/jphysiol.1979.sp012613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hansen O. Interaction of cardiac glycosides with (Na+ + K+)-activated ATPase. A biochemical link to digitalis-induced inotropy. Pharmacol Rev. 1984 Sep;36(3):143–163. [PubMed] [Google Scholar]
  9. Harik S. I., Doull G. H., Dick A. P. Specific ouabain binding to brain microvessels and choroid plexus. J Cereb Blood Flow Metab. 1985 Mar;5(1):156–160. doi: 10.1038/jcbfm.1985.20. [DOI] [PubMed] [Google Scholar]
  10. Harik S. I., Duckrow R. B., LaManna J. C., Rosenthal M., Sharma V. K., Banerjee S. P. Cerebral compensation for chronic noradrenergic denervation induced by locus ceruleus lesion: recovery of receptor binding, isoproterenol-induced adenylate cyclase activity, and oxidative metabolism. J Neurosci. 1981 Jun;1(6):641–649. doi: 10.1523/JNEUROSCI.01-06-00641.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harik S. I. Locus ceruleus lesion by local 6-hydroxydopamine infusion causes marked and specific destruction of noradrenergic neurons, long-term depletion of norepinephrine and the enzymes that synthesize it, and enhanced dopaminergic mechanisms in the ipsilateral cerebral cortex. J Neurosci. 1984 Mar;4(3):699–707. doi: 10.1523/JNEUROSCI.04-03-00699.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harik S. I., McGunigal T., Jr The protective influence of the locus ceruleus on the blood-brain barrier. Ann Neurol. 1984 Jun;15(6):568–574. doi: 10.1002/ana.410150609. [DOI] [PubMed] [Google Scholar]
  13. Harik S. I., Sharma V. K., Wetherbee J. R., Warren R. H., Banerjee S. P. Adrenergic and cholinergic receptors of cerebral microvessels. J Cereb Blood Flow Metab. 1981;1(3):329–338. doi: 10.1038/jcbfm.1981.36. [DOI] [PubMed] [Google Scholar]
  14. Harik S. I., Sharma V. K., Wetherbee J. R., Warren R. H., Banerjee S. P. Adrenergic receptors of cerebral microvessels. Eur J Pharmacol. 1980 Jan 25;61(2):207–208. doi: 10.1016/0014-2999(80)90168-5. [DOI] [PubMed] [Google Scholar]
  15. Heistad D. D. Summary of symposium on cerebral blood flow: effect of nerves and neurotransmitters. Cardiovascular Center, University of Iowa, Iowa City, Iowa, June 16--18, 1981. J Cereb Blood Flow Metab. 1981;1(4):447–450. doi: 10.1038/jcbfm.1981.50. [DOI] [PubMed] [Google Scholar]
  16. Henry D. P., Starman B. J., Johnson D. G., Williams R. H. A sensitive radioenzymatic assay for norepinephrine in tissues and plasma. Life Sci. 1975 Feb 1;16(3):375–384. doi: 10.1016/0024-3205(75)90258-1. [DOI] [PubMed] [Google Scholar]
  17. Herbst T. J., Raichle M. E., Ferrendelli J. A. beta-Adrenergic regulation of adenosine 3',5'-monophosphate concentration in brain microvessels. Science. 1979 Apr 20;204(4390):330–332. doi: 10.1126/science.34879. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. Nathanson J. A., Glaser G. H. Identification of beta-adrenergic-sensitive adenylate cyclase in intracranial blood vessels. Nature. 1979 Apr 5;278(5704):567–569. doi: 10.1038/278567a0. [DOI] [PubMed] [Google Scholar]
  20. Oldendorf W. H., Cornford M. E., Brown W. J. The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol. 1977 May;1(5):409–417. doi: 10.1002/ana.410010502. [DOI] [PubMed] [Google Scholar]
  21. Peroutka S. J., Moskowitz M. A., Reinhard J. F., Jr, Snyder S. H. Neurotransmitter receptor binding in bovine cerebral microvessels. Science. 1980 May 9;208(4444):610–612. doi: 10.1126/science.6102801. [DOI] [PubMed] [Google Scholar]
  22. Raichle M. E., Hartman B. K., Eichling J. O., Sharpe L. G. Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3726–3730. doi: 10.1073/pnas.72.9.3726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reese T. S., Karnovsky M. J. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967 Jul;34(1):207–217. doi: 10.1083/jcb.34.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schwartz A., Lindenmayer G. E., Allen J. C. The sodium-potassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol Rev. 1975 Mar;27(01):3–134. [PubMed] [Google Scholar]
  25. Sick T. J., Hertz L., LaManna J. C., Rosenthal M., Flaggman A., Harik S. I. Does endogenous norepinephrine regulate potassium homeostasis and metabolism in rat cerebral cortex? J Cereb Blood Flow Metab. 1982 Sep;2(3):355–361. doi: 10.1038/jcbfm.1982.36. [DOI] [PubMed] [Google Scholar]
  26. Swann A. C. Brain (Na+,K+)-ATPase and noradrenergic function: recovery of enzyme activity after norepinephrine depletion. Brain Res. 1984 Nov 12;321(2):323–326. doi: 10.1016/0006-8993(84)90186-0. [DOI] [PubMed] [Google Scholar]
  27. Swann A. C., Grant S. J., Maas J. W. Brain (Na+, K+)-ATPase and noradrenergic activity: effects of hyperinnervation and denervation on high-affinity ouabain binding. J Neurochem. 1982 Mar;38(3):836–839. doi: 10.1111/j.1471-4159.1982.tb08707.x. [DOI] [PubMed] [Google Scholar]
  28. Sweadner K. J. Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin. J Biol Chem. 1979 Jul 10;254(13):6060–6067. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES