AUTHOR=Thirunarayanan Nanthakumar , Raaka Bruce M., Gershengorn Marvin C.

TITLE=Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

JOURNAL=Frontiers in Endocrinology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2012.00120

DOI=10.3389/fendo.2012.00120

ISSN=1664-2392

ABSTRACT=<p>Taltirelin (TAL) is a thyrotropin-releasing hormone (TRH) analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R) in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating central nervous system effects in humans compared to TRH.</p>