Central penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult rat

GPE was rapidly metabolised in the plasma (8 min) after intraperitoneal administration. Despite having a short half-life in plasma, GPE was detected in the cerebrospinal fluid up to 40 min after intraperitoneal administration. With present of peptidase inhibitors, GPE existed in the brain tissue up to 3 h after intracerebroventricular administration, suggesting a role for peptolysis in its stability. The endopeptidase inhibitors 4- (2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) reduced GPE metabolism in the brain tissue while acid peptidase inhibitor pepstatin-A decreased GPE metabolism in the plasma. GPE reduced neuronal loss in the CA1-2 sub-region of the hippocampus given (intraperitoneally) after 30 min of hypoxic-ischemic injury in adult rats, further suggested the effectiveness of GPE central uptake. These results indicated that GPE crosses the blood-CSF and the functional CSF-brain barriers. The longer half-life of GPE in the CNS may be due to its unique enzymatic stability.