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Updated: Aug 12, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Constitutive activity of native thyrotropin-releasing hormone receptors revealed using a protein kinase C-responsive

A Jinsi-Parimoo1, M C Gershengorn

  • 1Department of Medicine, Cornell University Medical College, The New York Hospital, New York, New York 10021, USA.

Endocrinology
|April 1, 1997
PubMed

Insights

Native TRH receptors exhibit agonist-independent signaling, challenging previous assumptions. This constitutive activity, detected with a sensitive assay, is proportional to receptor expression and inhibited by antagonists.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cell Signaling

Background:

  • Thyrotropin-releasing hormone receptors (TRH-Rs) are G protein-coupled receptors.
  • TRH-Rs traditionally signal via the phosphoinositide pathway and are presumed inactive without an agonist.
  • A previously studied mutant TRH-R (C335Stop TRH-R) displayed constitutive signaling.

Purpose of the Study:

  • To investigate the basal signaling activity of native TRH receptors.
  • To determine if native TRH receptors exhibit agonist-independent signaling.
  • To compare the sensitivity of different signaling assays for detecting TRH-R activity.

Main Methods:

  • Utilized a protein kinase C-responsive reporter gene assay to measure TRH receptor signaling.
  • Expressed native mouse TRH receptors in COS-1 cells and Madin Darby canine kidney cells.
  • Tested the effect of benzodiazepine drugs as negative antagonists on TRH receptor activity.

Main Results:

  • Native mouse TRH receptors demonstrated agonist-independent signaling activity.
  • Signaling activity was directly proportional to the number of TRH receptors expressed.
  • Benzodiazepine drugs inhibited the constitutive activity of native TRH receptors.
  • Constitutive activity was observed in multiple cell lines, including those with endogenous TRH-Rs.

Conclusions:

  • Native TRH receptors possess inherent agonist-independent signaling capabilities.
  • The detection of constitutive TRH receptor activity is dependent on assay sensitivity.
  • TRH receptors may naturally oscillate between active and inactive states.

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