TY - JOUR
T1 - [β-glu2 ]trh is a functional antagonist of thyrotropin-releasing hormone (Trh) in the rodent brain
AU - Prokai-Tatrai, Katalin
AU - Nguyen, Vien
AU - Prokai, Laszlo
N1 - Funding Information:
Funding: This research was funded by The Welch Foundation (endowment BK-0031) and the National Institutes of Health (grant number MH059360).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Selective antagonists of thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2 ), in order to enable a better understanding of this peptide’s central functions, have not been identified. Using pGlu-Glu-Pro-NH2 ([Glu2 ]TRH) as a lead peptide and with modification at its central residue, our studies focused on some of its analogues synthesized as potential functional antagonists of TRH in the rodent brain. Among the peptides studied, the novel isomeric analogue [β-Glu2 ]TRH was found to suppress the analeptic and antidepressant-like pharmacological activities of TRH without eliciting intrinsic effects in these paradigms. [β-Glu2 ]TRH also completely reversed TRH’s stimulation of acetylcholine turnover in the rat hippocampus without a cholinergic activity of its own, which was demonstrated through in vivo microdialysis experiments. Altogether, [β-Glu2 ]TRH emerged as the first selective functional antagonist of TRH’s prominent cholinergic actions, by which this endogenous peptide elicits a vast array of central effects.
AB - Selective antagonists of thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2 ), in order to enable a better understanding of this peptide’s central functions, have not been identified. Using pGlu-Glu-Pro-NH2 ([Glu2 ]TRH) as a lead peptide and with modification at its central residue, our studies focused on some of its analogues synthesized as potential functional antagonists of TRH in the rodent brain. Among the peptides studied, the novel isomeric analogue [β-Glu2 ]TRH was found to suppress the analeptic and antidepressant-like pharmacological activities of TRH without eliciting intrinsic effects in these paradigms. [β-Glu2 ]TRH also completely reversed TRH’s stimulation of acetylcholine turnover in the rat hippocampus without a cholinergic activity of its own, which was demonstrated through in vivo microdialysis experiments. Altogether, [β-Glu2 ]TRH emerged as the first selective functional antagonist of TRH’s prominent cholinergic actions, by which this endogenous peptide elicits a vast array of central effects.
KW - Acetylcholine
KW - Analepsia
KW - Antidepressant
KW - Functional antagonist
KW - In vivo microdialysis
KW - Peptide analogues
KW - Thyrotropin-releasing hormone (TRH)
KW - [β-Glu ]TRH
UR - http://www.scopus.com/inward/record.url?scp=85107454730&partnerID=8YFLogxK
U2 - 10.3390/ijms22126230
DO - 10.3390/ijms22126230
M3 - Article
C2 - 34207724
AN - SCOPUS:85107454730
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
M1 - 6230
ER -