Proteolysis of Pro-Gly-Pro-Leu in the hippocampus, cerebellum, and cerebral cortex in rats after intravenous injection.
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.
Department of Chemistry of Physiologically Active Substances, Institute for Molecular Genetics, Russian Academy of Science, Moscow, Russia, ATCarma@mail.ru.
K V
KV
Shevchenko
T V
TV
V'yunova
L A
LA
Andreeva
I Yu
IY
Nagaev
V P
VP
Shevchenko
N F
NF
Myasoedov
D000818:Animals; D019540:Area Under Curve; D002531:Cerebellum / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D059748:Proteolysis; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D009842:Oligopeptides; C551701:prolyl-glycyl-prolyl-leucine