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. 2017 Mar;473(1):151-154. doi: 10.1134/S1607672917020168. Epub 2017 May 17.

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.

MeSH terms

  • Administration, Intranasal
  • Administration, Intravenous
  • Animals
  • Brain / metabolism*
  • Male
  • Oligopeptides / administration & dosage*
  • Oligopeptides / blood
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacokinetics
  • Permeability
  • Rats
  • Rats, Wistar

Substances

  • 5-oxoprolyl-arginyl-proline
  • Oligopeptides