2. Academic Validation
  3. Pharmacological Evaluation of Cannabinoid Receptor Modulators Using GRABeCB2.0 Sensor

Pharmacological Evaluation of Cannabinoid Receptor Modulators Using GRABeCB2.0 Sensor

  • Int J Mol Sci. 2024 May 3;25(9):5012. doi: 10.3390/ijms25095012.
Samay Shivshankar 1,  Josephine Nimely 1,  Henry Puhl 3rd 2,  Malliga R Iyer 1
Affiliations

Affiliations

  • 1 Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA.
  • 2 Laboratory of Biophotonics and Quantum Biology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA.
PMID: 38732230 DOI: 10.3390/ijms25095012
Abstract

Cannabinoid receptors CB1R and CB2R are G-protein coupled receptors acted upon by endocannabinoids (eCBs), namely 2-arachidonoylglycerol (2-AG) and N-arachidonoyl ethanolamine (AEA), with unique pharmacology and modulate disparate physiological processes. A genetically encoded GPCR activation-based sensor that was developed recently-GRABeCB2.0-has been shown to be capable of monitoring real-time changes in eCB levels in cultured cells and preclinical models. However, its responsiveness to exogenous synthetic cannabinoid agents, particularly antagonists and allosteric modulators, has not been extensively characterized. This current study expands upon the pharmacological characteristics of GRABeCB2.0 to enhance the understanding of fluorescent signal alterations in response to various functionally indiscriminate cannabinoid ligands. The results from this study could enhance the utility of the GRABeCB2.0 sensor for in vitro as well as in vivo studies of cannabinoid action and may aid in the development of novel ligands.

Keywords

2-AG; AEA; CB1R; CB2R; GRABeCB2.0; allosteric; orthosteric.

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