Proteolysis of Pro-Gly-Pro-Leu in Rat-Brain Hippocampus, Cerebellum, and Cortex Upon Intranasal Administration

Abstract

The concentrations of Pro-Gly-Pro-Leu (PGPL) tetrapeptide and its metabolites (Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro, and Pro-Gly) in various rat-brain compartments (hippocampus, cerebellum, cortex) were shown to be time-dependent after intranasal administration. The maximum concentrations of [ 3 H]-labeled PGPL and its degradation products in rat brain were observed after 40 min and amounted to 0.07% of the administered dose. The maximum concentrations of PGPL in the cerebellum, hippocampus, and cortex were 2.37, 1.93, and 0.67 pmol/g, respectively. The distribution in these brain compartments of PGPL proteolysis products differed from that of the initial peptide. The greatest amount of Gly-Pro-Leu was observed in the hippocampus with less in the cerebellum and cortex; of glyprolines (Pro-Gly-Pro, Pro-Gly, and Gly-Pro), in the cerebellum with less in the hippocampus and cortex. The contribution of one PGPL metabolic pathway or another to the formation from it of the set of shorter peptides in various rat-brain compartments was estimated based on the results.