title: Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor.
abstract: 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.
authors.affiliation: Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD, USA.
authors.forename: Nanthakumar
authors.initials: N
authors.lastname: Thirunarayanan
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Raaka
authors.forename: Marvin C
authors.initials: MC
authors.lastname: Gershengorn
keywords: human TRH receptor; taltirelin; thyrotropin-releasing hormone