Work

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

Year: 2012

Type: article

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.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2012.00120

Authors: Nanthakumar Thirunarayanan, Bruce M. Raaka, Marvin C. Gershengorn

Institutions: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801