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  • Meeting abstract
  • Open Access

The G protein-coupled receptor-associated protein 1 (GASP-1) regulates rimonabant-induced downregulation of GPR55

  • 1,
  • 1, 2,
  • 3 and
  • 1, 4Email author
BMC Pharmacology201111 (Suppl 2) :A57

  • Published:


  • Degradative Pathway
  • Receptor Recycling
  • Analgesic Tolerance
  • Tangible Evidence
  • GPR55 Agonist


The G protein-coupled receptor 55 (GPR55) has recently been suggested to be responsible for those cannabinoid responses that could not be attributed to either the cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor. Several potent GPR55 agonists were identified such as lysophosphatidylinositol (LPI) and several synthetic cannabinoids: One of these is rimonabant (SR141716A), an antagonist at the CB1 receptor, which showed clinical promise, but approval was revoked due to adverse events. Generally, the activity of G protein coupled receptors (GPCRs) is coordinated by receptor signalling, receptor desensitization and receptor resensitization. One regulatory mechanism to guarantee appropriate GPCR expression levels in physiological conditions is that of downregulating GPCRs via the G protein-coupled receptor-associated sorting protein 1 (GASP-1), thus leading to an attenuation of cellular signalling events. GASP-1 was originally found to target δ opioid receptors to lysosomes and, hence, to the degradative pathway. It was shown that GASP-1 is a key determinant in the development of analgesic tolerance to cannabinoids via its role in facilitating downregulation of the CB1 receptor.

Methods and results

By a variety of approaches we demonstrated that rimonabant promotes downregulation of GPR55 via GASP-1 in vitro and in vivo. We show that GPR55 interacts with GASP-1 in vitro and that disrupting the GPR55/GASP-1 interaction prevents post-endocytic receptor degradation, and thereby allows receptor recycling. Together, these data implicate GASP-1 as an important regulator of rimonabant-mediated downregulation of GPR55.


This work provides tangible evidence that GPR55 is degraded after prolonged agonist stimulation and that this mechanism is regulated by GASP-1.

Authors’ Affiliations

Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz, Austria
Present address: Molecular and Signal Transduction Section, Laboratory of Allergic Diseases,NIAID/NIH, Bethesda, MD 20892-1889, USA
Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA
Present address: Hagedorn Research Institute, Novo Nordisk A/S, 2820 Gentofte, Denmark


© Kargl et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.