TRH-like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain.
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.
Eugene Pekary
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Research Service, VA Greater Los Angeles Healthcare System and Department of Medicine, University of California, Los Angeles, CA 90073, USA. eugene.pekary@med.va.gov
Faull
Kym F
KF
Paulson
Mark
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Lloyd
Robert L
RL
Sattin
Albert
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D000818:Animals; D000928:Antidepressive Agents / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013550:Swimming / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry
D000928:Antidepressive Agents; D009842:Oligopeptides; D010446:Peptide Fragments; C506192:pyroglutamyltyroslyprolineamide; D013973:Thyrotropin-Releasing Hormone