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

• Main Authors: Nanthakumar eThirunarayanan, Bruce M. Raaka, Marvin C Gershengorn
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2012-10-01
• Series: Frontiers in Endocrinology
• Subjects: Thyrotropin-Releasing Hormone; trh; taltirelin; super-agonist; human TRH receptor
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00120/full

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 CNS effects in humans compared to TRH.