Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor
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 low...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-10-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00120/full |
| _version_ | 1819209049746440192 |
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| author | Nanthakumar eThirunarayanan Bruce M. Raaka Marvin C Gershengorn |
| author_facet | Nanthakumar eThirunarayanan Bruce M. Raaka Marvin C Gershengorn |
| author_sort | Nanthakumar eThirunarayanan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T05:49:06Z |
| format | Article |
| id | doaj.art-3bc5a9102cde479c8a94d4dab09eaa6d |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-23T05:49:06Z |
| publishDate | 2012-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-3bc5a9102cde479c8a94d4dab09eaa6d2022-12-21T17:58:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922012-10-01310.3389/fendo.2012.0012032644Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptorNanthakumar eThirunarayanan0Bruce M. Raaka1Marvin C Gershengorn2National Instititue of Diabetes and Digestive and Kidney DiseasesNational Instititue of Diabetes and Digestive and Kidney DiseasesNational Instititue of Diabetes and Digestive and Kidney DiseasesTaltirelin (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.http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00120/fullThyrotropin-Releasing Hormonetrhtaltirelinsuper-agonisthuman TRH receptor |
| spellingShingle | Nanthakumar eThirunarayanan Bruce M. Raaka Marvin C Gershengorn Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor Frontiers in Endocrinology Thyrotropin-Releasing Hormone trh taltirelin super-agonist human TRH receptor |
| title | Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor |
| title_full | Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor |
| title_fullStr | Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor |
| title_full_unstemmed | Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor |
| title_short | Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor |
| title_sort | taltirelin is a superagonist at the human thyrotropin releasing hormone receptor |
| topic | Thyrotropin-Releasing Hormone trh taltirelin super-agonist human TRH receptor |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2012.00120/full |
| work_keys_str_mv | AT nanthakumarethirunarayanan taltirelinisasuperagonistatthehumanthyrotropinreleasinghormonereceptor AT brucemraaka taltirelinisasuperagonistatthehumanthyrotropinreleasinghormonereceptor AT marvincgershengorn taltirelinisasuperagonistatthehumanthyrotropinreleasinghormonereceptor |