Skip to main content

Advertisement

Log in

An Inhibitory Role of Nitric Oxide in the Dynamic Regulation of the Blood-Brain Barrier Function

  • Rapid Communication
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

1. The present study aimed at elucidating the effect of nitric oxide (NO) on blood-brain barrier (BBB) function with mouse brain capillary endothelial (MBEC4) cells.

2. Histamine (20–100 μM) evoked NO production (1.6–7 μM) in MBEC4 cells in a dose-dependent manner.

3. The permeability coefficient of sodium fluorescein for MBEC4 cells and the cellular accumulation of rhodamine 123 in MBEC4 cells were increased dose-dependently by the addition of NO solutions (14 and 28 μM) every 10 min during a 30-min period.

4. The present study demonstrated that NO increased the permeability and inhibited the P-glycoprotein efflux pump of brain capillary endothelial cells, suggesting that NO plays an inhibitory role in the dynamic regulation of the BBB function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  • Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254.

    Article  PubMed  CAS  Google Scholar 

  • Daum, P. R., Downes, C. P., and Young, J. M. (1983). Histamine-induced inositol phosholipid break-down mirrors H1-receptor density in brain. Eur. J. Pharmacol. 87:497–498.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck, M.-P., Jolliet-Riant, P., Brée, F., Fruchart J.-C., Cecchelli, R., and Tillement, J.-P. (1992). Drug transfer across the blood-brain barrier: Correlation between in vitro and in vivo models. J. Neurochem. 58:1790–1797.

    Article  PubMed  CAS  Google Scholar 

  • Fontaine, M., Elmquist, W. F., and Miller, D. W. (1996). Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers. Life Sci. 59:1521–1531.

    Article  PubMed  CAS  Google Scholar 

  • Gimeno, G., Carpentier, P. H., Desquand-Billiald, S., Hanf, R., and Finet, M. (1998). l-arginine and NG-nitro-l-arginine methyl ester cause macromolecular extravasation in the microcirculation of awake hamsters. Eur. J. Pharmacol. 346:275–282.

    Article  PubMed  CAS  Google Scholar 

  • Hurst, R. D., and Fritz, I. B. (1996). Properties of an immortalized vascular endothelial/glioma cell co-culture model of blood-brain barrier. J. Cell. Physiol. 167:81–88.

    Article  PubMed  CAS  Google Scholar 

  • Hurst, R. D., Azam, S., Hurst, A., and Clark, J. B. (2001). Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood-brain barrier. Brain Res. 894:181–188.

    Article  PubMed  CAS  Google Scholar 

  • Ikesue, H., Kataoka, Y., Kawachi, R., Dohgu, S., Shuto, H., and Oishi, R. (2000). Cyclosporine enhances α1-adrenoceptor-mediated nitric oxide production in C6 glioma cells. Eur. J. Pharmacol. 407:221–226.

    Article  PubMed  CAS  Google Scholar 

  • Kishi, F., Nakaya, Y., Takahashi, A., Miyoshi, H., Nomura, M., and Saito, K. (1996). Intracellular and extracellular Ca2+ regulate histamine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes. Pharmacol. Res. 33:123–126.

    Article  PubMed  CAS  Google Scholar 

  • Kusuhara, H., and Sugiyama, Y. (2001). Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1). Drug. Discov. Today 6:150–156.

    Article  PubMed  CAS  Google Scholar 

  • Mayhan, W. G. (1996). Role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier. Brain Res. 743:70–76.

    Article  PubMed  CAS  Google Scholar 

  • Mayhan, W. G. (2000). Nitric oxide donor-induced increase in permeability of the blood-brain barrier. Brain Res. 866:101–108.

    Article  PubMed  CAS  Google Scholar 

  • Menconi, M. J., Unno, N., Smith, M., Aguirre, D. E., and Fink, M. P. (1998). Nitric oxide donor-induced hyperpermeability of cultured intestinal epithelial monolayers: Role of superoxide radical, hydroxyl radical, and peroxynitrite. Biochim. Biophys. Acta 1425:189–203.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M. (1999). Blood-brain barrier biology and methodology. J. Neurovirol. 5:556–569.

    PubMed  CAS  Google Scholar 

  • Shukula, A., Dikshit, M., and Srimal, R. C. (1996). Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain. Experientia 52:136–140.

    Article  Google Scholar 

  • Tatsuta, T., Naito, M., Oh-hara, T., Sugawara, I., and Tsuruo, T. (1992). Functional involvement of P-glycoprotein in blood-brain barrier. J. Biol. Chem. 267:20383–20391.

    PubMed  CAS  Google Scholar 

  • Tatsuta, T., Naito, M., Mikami, K., and Tsuruo, T. (1994). Enhanced expression by the brain matrix of P-glycoprotein in brain capillary endothelial cells. Cell Growth Differ. 5:1145–1152.

    PubMed  CAS  Google Scholar 

  • Trevin, S., Kataoka, Y., Kawachi, R., Shuto, H., Kumakura, K., and Oishi, R. (1998). Direct and continuous electrochemical measurement of noradrenaline-induced nitric oxide production in C6 glioma cells. Cell. Mol. Neurobiol. 18:453–458.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, A., and Tamai, I. (1999). Carrier-mediated or specialized transport of drugs across the blood-brain barrier. Adv. Drug. Deliv. Rev. 36:277–290.

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

This work was supported in part by Grants-in-Aid for Scientific Research ((B)(2) 14370789) and ((C)(2) 15590475) from JSPS, Japan, by a Grant-in-Aid for Exploratory Research (16659138) from MEXT, Japan, and by funds (No.: 031001) from the Central Research Institute of Fukuoka University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yasufumi Kataoka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamauchi, A., Dohgu, S., Nishioku, T. et al. An Inhibitory Role of Nitric Oxide in the Dynamic Regulation of the Blood-Brain Barrier Function. Cell Mol Neurobiol 27, 263–270 (2007). https://doi.org/10.1007/s10571-007-9139-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-007-9139-z

KEY WORDS

Navigation