(1272-A) Differential binding of ∆9-tetrahydrocannabinol derivatives to type 1 cannabinoid receptors (CB1)
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Cannabinoid receptors are G protein-coupled receptors (GPCRs) that lead to diverse cellular events mediated through different cell signaling pathways. Two main types of cannabinoid receptors exist: CB1 and CB2. CB1 receptors are mainly found in the brain and central nervous system, where they play a role in regulating mood, memory, pain, appetite and motor function. CB2 receptors reside in the immune system and peripheral tissues and are mainly linked to modulating inflammation, immune responses and other functions of the body’s defence system. Cannabinoids are potential tools to combat a variety of diseases including different neurological or metabolic conditions. This interest is driving efforts to understand the pharmacology of naturally occurring and synthetic cannabinoids at the receptor level. The results to date show that when different cannabinoids bind to their receptors, they produce distinct effects depending on which signaling pathway is activated. Moreover, the signaling pathway activation depends on the agonist structure and the monomeric or heteromeric cannabinoid receptor states. Here, a microplate reader was used to detect differential binding of natural cannabinoids to CB1 based on TR-FRET assays using terbium and the CELT-335 fluorescent ligand. CELT-335 is a full agonist that binds to the orthosteric site of human cannabinoid receptors and bears a highly hydrophilic fluorophore compatible with TR-FRET. The tagged agonist binds tightly to the CB1 GPCR labelled with terbium. When agonist and receptor come into proximity, energy is transferred based on a spectral overlap of terbium emission and CELT-335 excitation and light is emitted at 665 nm with terbium as the TR-FRET donor..CELT-335 showed high affinity for the CB1 cannabinoid receptor subtype and enabled binding affinity values to be obtained for Δ9-THC, Δ9-THCA and Δ9-THCV that were comparable to values reported in the literature.