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Updated: Aug 8, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
11:45

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

Protein kinase A-dependent coupling of mouse prostacyclin receptors to Gi is cell-type dependent

Kevin B S Chow1, Robert L Jones, Helen Wise

  • 1Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

European Journal of Pharmacology
|August 12, 2003
PubMed

Insights

Cicaprost activates Gs and Gq/11 signaling pathways via prostacyclin (IP) receptors in various cells. However, no evidence suggests IP receptor coupling to Gi-mediated pathways.

Area of Science:

  • Pharmacology
  • Cellular Biology
  • Molecular Signaling

Background:

  • The prostacyclin (IP) receptor plays a crucial role in cardiovascular and cellular functions.
  • Understanding IP receptor signaling pathways is essential for developing targeted therapeutics.
  • Previous studies suggest IP receptor activation can modulate various intracellular signaling cascades.

Purpose of the Study:

  • To investigate the ability of the IP receptor agonist cicaprost to activate Gs-, Gq/11-, and Gi-mediated cell signaling pathways.
  • To compare cicaprost's signaling effects on cells expressing cloned human (hIP) and mouse (mIP) IP receptors versus cells with endogenous IP receptors.
  • To determine the specific G protein coupling profiles of the human and mouse IP receptors.

Main Methods:

  • Utilized Chinese hamster ovary (CHO) and human embryonic kidney 293 (HEK 293) cells expressing cloned hIP or mIP receptors.
  • Examined signaling in NG108-15 and SK-N-SH cells with endogenous IP receptors.
  • Measured [3H]cyclic AMP and [3H]inositol phosphate production in response to cicaprost stimulation.
  • Assessed the effect of cicaprost on forskolin-stimulated [3H]cyclic AMP production.

Main Results:

  • Cicaprost stimulated [3H]cyclic AMP production with EC50 values ranging from 1.5-22 nM across tested cell lines.
  • Cicaprost stimulated [3H]inositol phosphate production with EC50 values of 49-457 nM in most cell lines, excluding SK-N-SH cells.
  • Cicaprost failed to inhibit forskolin-stimulated [3H]cyclic AMP production, indicating no coupling to Gi.
  • Both hIP and mIP receptors demonstrated cell type-dependent coupling to Gs and Gq/11 pathways.

Conclusions:

  • Human and mouse IP receptors effectively couple to Gs and Gq/11 signaling pathways.
  • The coupling of IP receptors to these pathways is dependent on the cell type.
  • No evidence was found to support IP receptor coupling to Gi-mediated signaling pathways.

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