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GPR55 ligands promote receptor coupling to multiple signalling pathways
Open accessAbstract
Background and purpose: Although GPR55 is potently activated by the endogenous lysophospholipid, L‐α‐lysophosphatidylinositol (LPI), it is also thought to be sensitive to a number of cannabinoid ligands, including the prototypic CB1 receptor antagonists AM251 and SR141716A (Rimonabant®). In this study we have used a range of functional assays to compare the pharmacological activity of selected cannabinoid ligands, AM251, AM281 and SR141716A with LPI in a HEK293 cell line engineered to stably express recombinant, human GPR55. Experimental approach: We evaluated Ca 2+ signalling, stimulation of extracellular signal regulated kinase (ERK1/2) mitogen activated kinase MAP‐kinases, induction of transcriptional regulators that are downstream of GPR55, including nuclear factor of activated T cells (NFAT), nuclear factor‐κB (NF‐κB) and cAMP response element binding protein (CREB), as well as receptor endocytosis. In addition, we assessed the suitability of a novel, label‐free assay for GPR55 ligands that involves optical measurement of dynamic mass redistribution following receptor activation. Key results: GPR55 linked to a range of downstream signalling events and that the activity of GPR55 ligands was influenced by the functional assay employed, with differences in potency and efficacy observed. Conclusions and implications: Our data help to resolve some of the issues surrounding the pharmacology of cannabinoid ligands at GPR55 and highlight some differences in effector coupling associated with distinct GPR55 ligands.
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The orphan receptor GPR55 is a novel cannabinoid receptor
Ryberg, E., Larsson, N., Sjögren, S., Hjorth, S., Hermansson, N., Leonova, J., Elebring, T., Nilsson, K., Drmota, T., & Greasley, P. J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707460 · Cited by 1,568
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Cited by
Pellati, F., Borgonetti, V., Brighenti, V., Biagi, M., Benvenuti, S., & Corsi, L. (2018) · BioMed Research International · doi:10.1155/2018/1691428 · Cited by 371
Petrosino, S., & Di Marzo, V. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13580 · Cited by 328
G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus
Riddy, D. M., Delerive, P., Summers, R. J., Sexton, P. M., & Langmead, C. J. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014373 · Cited by 108
Merighi, S., Gessi, S., Varani, K., Fazzi, D., Mirandola, P., & Borea, P. A. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01948.x · Cited by 79
Cannabinoids: new promising agents in the treatment of neurological diseases.
Giacoppo, S., Mandolino, G., Galuppo, M., Bramanti, P., & Mazzon, E. (2014) · Molecules · doi:10.3390/molecules191118781 · Cited by 79
Metadata
- Authors
- Henstridge, C. M., Balenga, N. A., Schröder, R., Kargl, J. K., Platzer, W., Martini, L., Arthur, S., Penman, J., Whistler, J. L., Kostenis, E., Waldhoer, M., & Irving, A. J.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2010-05-19
- Volume
- 160
- Issue
- 3
- Pages
- 604-614
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W1887249759
- Cited by
- 209
- References
- 2
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Henstridge, C. M., Balenga, N. A., Schröder, R., Kargl, J. K., Platzer, W., Martini, L., Arthur, S., Penman, J., Whistler, J. L., Kostenis, E., Waldhoer, M., & Irving, A. J. (2010). GPR55 ligands promote receptor coupling to multiple signalling pathways. British Journal of Pharmacology. https://doi.org/10.1111/j.1476-5381.2009.00625.x
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