Abstract
It was shown that the neuroactive peptide 5-oxo-Pro-Arg-Pro (5-oxo-PRP) is detected in the brain in the time interval of 5–120 min after it was intravenously or intranasally administered to rats; the maximum concentration of labeled tripeptide in these modes of administration was observed after 30 and 10 min, respectively. A significant difference in the concentrations of 5-oxo-PRP in the blood and brain (the latter was 50 times lower) during intravenous administration indicates a relatively low permeability of the peptide across the blood–brain barrier. Pharmacokinetic data analysis showed that, when administered intranasally, approximately 45% of the total number of 5-oxo-PRP detectable in the brain in the entire period of study enters via transport from the nasal cavity, and the rest of the peptide enters through the blood–brain barrier from the blood stream. It was found that 5-oxo-PRP in rats is rapidly metabolized forming proteolytic products, mainly amino acids, and degradation products, presumably oxidized these amino acids.
Similar content being viewed by others
References
Fosgerau, K. and Hoffmann, T., Drug Discov. Today, 2015, vol. 20, no. 1, pp. 122–128.
Lyapina, L.A., Grigor’eva, M.E., Obergan, T.Yu., Shubina, T.A., Andreeva, L.A., and Myasoedov, N.F., Biol. Bull., 2015, vol. 42, no. 6, pp. 546–555.
Peptide Chemistry and Drug Design, Dunn, B.M., Ed., New York: Wiley, 2015.
Myasoedov, N.F., Lyapina, L.A., Grigorjeva, M.E., Obergan, T.Y., Shubina, T.A., and Andreeva, L.A., Pathophysiology, 2016, vol. 23, no. 1, pp. 27–33.
V'yunova, T.V., Andreeva, L.A., Shevchenko, K.V., Shevchenko, V.P., and Myasoedov, N.F., J. Neurochem., 2016, vol. 33, no. 3, pp. 219–225.
Shevchenko, V.P., Nagaev, I.Yu., Andreeva, L.A., and Myasoedov, N.F., Dokl. Biochem. Biophys., 2017 (in press).
Shevchenko, K.V., V’yunova, T.V., Andreeva, L.A., Nagaev, I.Yu., Shevchenko, V.P., and Myasoedov, N.F., Dokl. Biochem. Biophys., 2014, vol. 456, pp. 111–115.
Shevchenko, K.V., V’yunova, T.V., Radilov, A.S., Andreeva, L.A., Nagaev, I.Yu., Shevchenko, V.P., Rembovskii, V.R., and Myasoedov, N.F., Dokl. Biochem. Biophys., 2015, vol. 465, pp. 435–439.
Shevchenko, K.V., Nagaev, I.Yu., Babakov, V.N., Andreeva, L.A., Shevchenko, V.P., Radilov, A.S., and Myasoedov, N.F., Dokl. Biochem. Biophys., 2015, vol. 464, pp. 301–304.
Karkishchenko, N.N., Khoron’ko, V.V., Sergeeva, S.A., and Karkishchenko, V.N., Farmakokinetika (Pharmacokinetics), Rostov-on-Don: Feniks (Ser. Gippokrat), 2001.
Charlton, S.T., Whetstone, J., Fayinka, S.T., Read, K.D., Illum, L., and Davis, S.S., Pharm. Res., 2008, vol. 25, no. 7, pp. 1531–1543.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © K.V. Shevchenko, I.Yu. Nagaev, V.P. Shevchenko, L.A. Andreeva, S.I. Shram, N.F. Myasoedov, 2017, published in Doklady Akademii Nauk, 2017, Vol. 473, No. 6, pp. 742–745.
Rights and permissions
About this article
Cite this article
Shevchenko, K.V., Nagaev, I.Y., Shevchenko, V.P. et al. The penetration of 5-oxo-Pro-Arg-Pro into the brain and the major metabolic pathways of this peptide in the rat brain and blood at the intranasal and intravenous administration. Dokl Biochem Biophys 473, 151–154 (2017). https://doi.org/10.1134/S1607672917020168
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1607672917020168