Proteolysis of Pro-Gly-Pro-Leu in the hippocampus, cerebellum, and cerebral cortex in rats after intravenous injection

Bull Exp Biol Med. 2014 Nov;158(1):37-41. doi: 10.1007/s10517-014-2686-7. Epub 2014 Nov 19.

Abstract

We studied the dependence of the levels of Pro-Gly-Pro-Leu peptide and its metabolites (Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly) from the time of administration in the hippocampus, cerebellum, and cerebral cortex of rats. After intravenous injection of Pro-Gly-Pro-Leu, the maximum concentration of metabolites in the rat brain was found in 20-min sample (0.026% from the amount of introduced labeled tetrapeptide); it was by 2.6 times higher that after intranasal administration. The calculated ratios of the peptide content (AUC) in brain structures for Pro-Gly-Pro-Leu and its metabolites after intranasal and intravenous injection were in most cases >1; hence, the levels of these peptides in the cerebellum, hippocampus, and brain cortex after intravenous injection were slightly higher than after intranasal administration. From these data, content of Pro-Gly-Pro-Leu and its metabolites per 1 g of the cerebellum, hippocampus and cortex was calculated: the maximum concentrations of Pro-Gly-Pro-Leu in the cerebellum, hippocampus, and cortex were 15.63, 18.48, and 2.95 pmol/g, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Cerebellum / metabolism*
  • Hippocampus / metabolism*
  • Injections, Intravenous
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacokinetics*
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics*
  • Proteolysis
  • Rats, Wistar

Substances

  • Neuroprotective Agents
  • Oligopeptides
  • prolyl-glycyl-prolyl-leucine