Low affinity analogs of thyrotropin-releasing hormone are super-agonists

Stanislav Engel, Susanne Neumann, Navneet Kaur, Vikramdeep Monga, Rahul Jain, John Northup, Marvin C. Gershengorn

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We show that several analogs of thyrotropin-releasing hormone (TRH) are more efficacious agonists at TRH receptors R1 and R2 than TRH itself. The apparent efficacies of the analogs were inversely related to their potencies and were independent of the nature of the modifications in TRH structure. In studies in intact cells, we showed that the differences in apparent efficacies were not due to differences in G-protein coupling, receptor desensitization, or recycling. Moreover, the differences in efficacies persisted in experiments using accessory protein-free membranes. We conclude that the efficacy differences of TRH analogs originated from the enhanced ability of TRH-R complexed to the low affinity agonists to directly activate G-protein(s), and not by amodulation of the activity of accessory proteins, and propose possible mechanisms for this phenomenon.

Original languageEnglish
Pages (from-to)13103-13109
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number19
DOIs
StatePublished - 12 May 2006
Externally publishedYes

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