In vitro neuroprotection against glutamate-induced toxicity by pGlu-Glu-Pro-NH(2) (EEP).

EEP is a tripeptide structurally similar to thyrotropin releasing hormone (TRH) and, like TRH, it is found in the mammalian brain. TRH has been found to increase in brain regions after seizures and to be neuroprotective. EEP has also been shown to increase in brain regions following seizure activity. We therefore sought to determine whether the similarities between these two peptides might be extended to include neuroprotection. Both TRH and EEP were found to be neuroprotective in vitro against an excitotoxic insult. Interestingly, the two tripeptides appeared to have different mechanisms of action. Even though EEP was as much as four times more neuroprotective than TRH, its ability to reduce glutamate-stimulated increases in intraneuronal Ca(2+) was about half that of TRH.