Overexpression of orphan receptor GPR61 increases cAMP levels upon forskolin stimulation in HEK293 cells: in vitro and in silico validation of 5-(nonyloxy)tryptamine as a low-affinity inverse agonist

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Colleges, School and Institutes

External organisations

  • Department of Physiology and Pharmacology, Karolinska Insitutet, Solna, Stockholm, Sweden, pawel.kozielewicz@ki.se.
  • Chair of Physical Pharmacy and Bioanalysis, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.


GPR61 is an orphan receptor that belongs to Class A of G-protein-coupled receptors. It has been reported that GPR61 has a constitutive activity and couples to Gαs. In the present study, we characterized GPR61 function and ligand binding by experimental and molecular docking studies. We demonstrated that heterologous expression of GPR61 in HEK293 cells enhanced the cAMP synthesis response to forskolin, whereas the basal cAMP synthesis was unaffected. 5-(Nonyloxy)tryptamine inhibited forskolin-stimulated cAMP production in GPR61-expressing HEK293 cells. These studies highlight that the intrinsic activity of this receptor is only measurable following its synergy with Gαs.

Bibliographic note

© 2019 S. Karger AG, Basel.


Original languageEnglish
Number of pages6
Publication statusPublished - 26 Jul 2019


  • Constitutive activity, GPR61, Inverse agonist, Molecular modeling, Proteins, Receptor

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