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

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.