Significance of the Second Messenger Molecules in the Regulation of Cerebral Endothelial Cell Functions

An Overview
  • Ferenc Joó
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)


Several receptors for different vasoactive substances have been shown to be coupled to the microvascular adenylate cyclase and to increase the intraendothelial amount of cyclic AMP (Joó, 1986, 1992, 1993). As a consequence of elevated intraendothelial cyclic AMP, changes in permeability (Joó, 1972; Rubin et al. 1991), in endothelial growth and differentiation (Kempski et al. 1987), in nitric oxide and endothelin secretions (Durieu-Trautmann et al. 1993) and in a hyperpolarization-activated current carried by both Na+ and K+ ions (Janigro et al. 1994) have been reported. Elevations of cyclic AMP concentrations may be important in regulating the endothelial barrier in two-ways: (i) by narrowing the paracellular pathways for small molecular weight substances (Rubin et al. 1991), and (ii) activating the transendothelial transport for macromolecules (Joó, 1972). Recently, Grammas et al. (1994) found significantly elevated cAMP levels in microvessels from Alzheimer’s disease compared to nondemented elderly controls.


Atrial Natriuretic Peptide Guanylate Cyclase Brain Capillary Endothelial Cell Cerebral Endothelial Cell Brain Microvessel Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Catalan, R.E., A.M. Martinez, M.D. Aragonés, and I. Fernandez (1989) Substance P stimulates translocation of protein kinase C in brain microvessels. Biochem.Biophys.Res.Commun. 164: 595–600.PubMedCrossRefGoogle Scholar
  2. Deli, M., M.-P. Dehouck, R. Cecchelli, C.S. Abraham, and F. Joó (1995) Histamine induces a selective albumin permeation through the blood-brain barrier in vitro. Inflammation Res. 44: S56 - S57.CrossRefGoogle Scholar
  3. Deli, M., F. Joó, I. Krizbai, I. Lengyel, M.G. Nunzi, and J.R. Wolff (1993) Calcium/calmodulin-stimulated protein kinase II is present in primary cultures of cerebral endothelial cells. J.Neurochem. 60: 1960–1963.PubMedCrossRefGoogle Scholar
  4. Dóczi, T., F. Joó, P. Szerdahelyi, and M. Bodosi (1987) Regulation of brain water and electrolyte contents: the possible involvement of central atrial natriuretic factor. Neurosurgery 21: 454–458.PubMedCrossRefGoogle Scholar
  5. Drewes, L.R., M.A. Broderius, and D.Z. Gerhart (1988) Phorbol ester stimulates hexose uptake by brain microvessel endothelial cells. Brain Res.Bull. 21: 771–776.PubMedCrossRefGoogle Scholar
  6. Durieu-Trautmann, O., C. Fédérici, C. Créminon, N. Foignant-Chaverot, F. Roux, M. Claire, A.D. Strosberg, and P.O. Couraud (1993) Nitric oxide and endothelin secretion by brain microvessel endothelial cells: Regulation by cyclic nucleotides. J. Cellular Physiol. 155: 104–111.CrossRefGoogle Scholar
  7. Dux, E. and F. Joó (1982) Effects of histamine on brain capillaries: fine structural and immunohistochemical studies after intracarotid infusion. Exptl.Brain Res. 47: 252–258.CrossRefGoogle Scholar
  8. Dux, E., P. Temesvari, F. Joó, G. Adam, F. Clementi, L. Dux, J. Hideg, and K.A. Hossmann (1984) The blood-brain barrier in hypoxia: ultrastructural aspects and adenylate cyclase activity of brain capillaries. Neuroscience 12: 951–958.PubMedCrossRefGoogle Scholar
  9. Dux, E., P. Temesvari, P. Szerdahelyi, A. Nagy, J. Kovacs, and F. Joó (1987) Protective effect of antihistamines on cerebral oedema induced by experimental pneumothorax in newborn piglets. Neuroscience 22: 317–321.PubMedCrossRefGoogle Scholar
  10. Ehrlich, P. (1885) Das Sauerstoff-bedürfnis des Organismus. Eine farbenanalytische Studie.Google Scholar
  11. Berlin: A. Hirschwald. Grammas, P., A.E. Roller, and M.J. Ball (1994) Increased accumulation of cAMPin cerebral microvessels in Alzheimer disease. Neurobiol. of Aging 15: 113–116.Google Scholar
  12. Guillot, F.L., K.L. Audus, and T.J. Raub (1990) Fluid-phase endocytosis by primary cultures of bovine brain microvessel endothelial cell monolayers. Microvasc.Res. 39: 1–14.PubMedCrossRefGoogle Scholar
  13. Homayoun, P., W.D. Lust, and S.I. Harik (1989) Effect of several vasoactive agents on guanylate cyclase activity in isolated rat brain microvessels. Neurosci.Lett. 107: 273–278.PubMedCrossRefGoogle Scholar
  14. Huszti, Z., M.A. Deli, and F. Joó (1995) Carrier-mediated uptake and release of histamine by cultured rat cerebral endothelial cells. Neurosci. Letters 184: 185–188.CrossRefGoogle Scholar
  15. Ibaragi, M., M. Niwa, and M. Ozaki (1989) Atrial natriuretic peptide modulates amiloride-sensitive Na+ transport across the blood-brain barrier. J.Neurochem. 53: 1802–1806.PubMedCrossRefGoogle Scholar
  16. Janigro, D., G.A. West, T.-S. Nguyen, and H.R. Winn (1994) Regulation of blood-brain barrier endothelial cells by nitric oxyde. Circ. Res. 75: 528–538.PubMedCrossRefGoogle Scholar
  17. Joó, F. (1972) Effect of N6,06-dibutyril cyclic 3’,5’-adenosine monophosphate on the pinocytosis of brain capillaries in mice. Experientia 28: 1470–1471.PubMedCrossRefGoogle Scholar
  18. Joó, F. (1986) New aspects to the function of cerebral endothelium. Nature 321: 197–198.PubMedCrossRefGoogle Scholar
  19. Joó, F. (1992) The cerebral microvessels in tissue culture. an update. J.Neurochem. 58: 1–17.PubMedCrossRefGoogle Scholar
  20. Joó, F. (1993) The blood-brain barrier in vitro: The second decade. Neurochem. Int. 23: 499–521.PubMedCrossRefGoogle Scholar
  21. Joó, F. and I. Klatzo (1989) Role of cerebral endothelium in brain oedema. Neurol.Res. 11: 67–75.PubMedGoogle Scholar
  22. Karnushina, I.L., J.M. Palacios, G. Barbin, E. Dux, F. Joó, and J.C. Schwartz (1980) Studies on a capillary-rich fraction isolated from brain: histaminic components and characterization of the histamine receptors linked to adenylate cyclase. J.Neurochem. 34: 1201–1208.Google Scholar
  23. Kempski, O., B. Wroblewska, and M. Spatz (1987) Effects of forskolin on growth and morphology of cultured glial and cerebrovascular endothelial and smooth muscle cells. Int.J.Dev.Neurosci. 5: 435–445.PubMedCrossRefGoogle Scholar
  24. Krizbai, I., G. Szabó, M. Deli, K. Maderspach, C. Lehel, Z. Olah, J.R. Wolff, and F. Joó (1995) Expression of protein kinase C family members in the cerebral endothelial cells. J. Neurochem. 65: 495–462.Google Scholar
  25. Lane, T.A., G.E. Lamkin, and E. Wancewicz (1989) Modulation of endothelial cell expression of intracellular adhesion molecule 1 by protein kinase C activation. Biochem.Biophys.Res.Commun. 161: 945–952.PubMedCrossRefGoogle Scholar
  26. Markovac, J. and G.W. Goldstein (1988) Transforming growth factor beta activiates protein kinase C in microvessels isolated from immature rat brain. Biochem.Biophys.Res.Commun. 150: 575–582.PubMedCrossRefGoogle Scholar
  27. Marsault, R. and C. Frelin (1992) Activation by nitric oxyde of guanylate cyclase in endothelial cells from brain capillaies. J.Neurochem. 59: 942–945.PubMedCrossRefGoogle Scholar
  28. Palmer, G.C. (1981) Distribution of guanylate cyclase in rat cerebral cortex: neuronal, glial, capillary, pia-arachnoid and synaptosomal fractions plus choroid plexus. Neuroscience 6: 2547–2553.PubMedCrossRefGoogle Scholar
  29. Revest, P.A., N.J. Abbott, and J.I. Gillespie (1991) Receptor mediated changes in intracellular Cat’ in cultured rat brain capillary endothelial cells. Brain Res. 549: 159–161.PubMedCrossRefGoogle Scholar
  30. Rubin, L.L., D.E. Hall, S. Porter, K. Barbu, C. Cannon, H.C. Homer, M. Janatpour, C.W. Liaw, K. Manning, J. Morales, L.I. Tanner, J. Tomaselli, and F. Bard (1991) A cell culture model of the blood-brain barrier. J.Cell.Biol. 115: 1725–1735.PubMedCrossRefGoogle Scholar
  31. Tdsaki, A., P. Szerdahelyi, and F. Joó (1994) Treatment with ranitidine of ischemic brain edema. Eur.J.Pharm. 264: 455–458.CrossRefGoogle Scholar
  32. Vigne, P., L. Lund, and C. Frelin (1994) Cross talk among cyclic AMP, cyclic GMP, and Ca2+-dependent intracellular signalling mechanisms in brain capillary endothelial cells. J. Neurochem. 62: 2269–2274.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Ferenc Joó
    • 1
  1. 1.Laboratory of Molecular NeurobiologyInstitute of Biophysics Biological Research CenterSzegedHungary

Personalised recommendations