TRH‐like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain

Abstract

Abstract We have previously reported the occurrence of pGlu‐Glu‐Pro‐NH 2 (Glu‐TRH, EEP), Val‐TRH, Tyr‐TRH, Leu‐TRH, Phe‐TRH, and Trp‐TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross‐react with the general structure pGlu‐X‐Pro‐NH 2 where ‘X’ maybe any amino acid residue ( Peptides 2004; 25 : 647). This new family of TRH‐like peptides, along with TRH (pGlu‐His‐Pro‐NH 2 ), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti‐amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr‐TRH and Phe‐TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr‐TRH in rat brain. Furthermore, synthetic Tyr‐TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties. Copyright © 2005 John Wiley & Sons, Ltd.