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Opioid receptor-like (ORL1) receptor utilizes both G(oA) and G(oB) for signal transduction

Prudence H Tso1, Yung H Wong

  • 1Department of Biochemistry, the Molecular Neuroscience Center, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Protein and Peptide Letters
|June 28, 2006
PubMed

Insights

ORL1 receptors can inhibit adenylyl cyclase and stimulate ERKs using PTX-resistant G proteins. However, chronic activation leads to PTX-sensitive adenylyl cyclase superactivation and loss of ERK responsiveness.

Area of Science:

  • Pharmacology
  • Cell Signaling
  • Molecular Biology

Background:

  • The ORL1 receptor is a G protein-coupled receptor involved in various physiological processes.
  • Understanding its signaling pathways is crucial for developing targeted therapeutics.

Purpose of the Study:

  • To investigate the signaling mechanisms of ORL1 receptors, particularly their interaction with G proteins.
  • To elucidate the role of pertussis toxin (PTX)-sensitive and -resistant pathways in ORL1 receptor function.

Main Methods:

  • Stable expression of ORL1 receptors in HEK 293 cells.
  • Utilized PTX-resistant mutants of Galpha(oA/B) to study signal transduction.
  • Assessed adenylyl cyclase (AC) activity and extracellular signal-regulated kinase (ERK) phosphorylation.

Main Results:

  • ORL1 receptors coupled to PTX-resistant Galpha(oA/B) mutants inhibited AC and stimulated ERKs.
  • Chronic ORL1 receptor activation resulted in PTX-sensitive AC superactivation.
  • Loss of ERK1/2 responsiveness was observed during chronic activation, which was also PTX-sensitive.

Conclusions:

  • ORL1 receptor signaling involves both PTX-sensitive and -resistant pathways.
  • Chronic activation induces distinct adaptive changes in AC and ERK signaling.
  • These findings highlight the complexity of G protein-coupled receptor regulation.

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