Galanin GPCR Assays
Background of Galanin Receptors
Galanin receptors are a family of G protein-coupled receptors activated by endogenous ligand galanin and galanin-like peptides. Galanin is a neuropeptide responsible for many biological activities, especially neurological activities, and endocrine processes. Galanin is capable of inhibiting acetylcholine release in the central nervous system (CNS). It has been indicated that galanin may play an essential role in cholinergic dysfunction in Alzheimer's disease. Besides, galanin is also responsible for gastrointestinal motility, learning and memory, spinal reflex, and epileptic activity, as well as hormone regulation of growth hormone, prolactin, and luteinizing hormone.
Fig.1 Schematic illustration of the three galanin receptor subtypes (GAL1, GAL2, and GAL3) and their transduction mechanisms. (Ögren, 2006)
Distribution and Function of Galanin Receptors
Galanin receptors are wildly expressed in CNS. Besides, they are also located in the pancreas, gastrointestinal tract, heart, and skin. According to the galanin GPCR-mediated signaling pathways, the treatments for many related diseases and disorders, such as Alzheimer's disease, neuropathic pain, epilepsy, diabetes, addiction, and cancer, could be established.
Subtypes and Mechanisms of Galanin Receptors
The galanin receptor family contains three subtypes of G protein-coupled receptors, including GAL1, GAL2, and GAL3. The signal transduction of GAL1 and GAL3 is mediated by Gi/Go, while GAL2 receptors couple Gq/G11.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| GAL1 receptor | GALR1 |
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| GAL2 receptor | GALR2 |
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| GAL3 receptor | GALR3 |
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Assay List of Galanin Receptors
Creative Biolabs can provide a range of assays of galanin receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors |
| Journal | Nature communications |
| Published | 2022 |
| Abstract | Galanin is a 30-amino acid neuropeptide widely distributed in the nervous systems and co-exists with numerous classical neurotransmitters and neuropeptides. Galanin plays a role in regulating metabolic homeostasis, reproduction, nociception, arousal/sleep, cognition, and stemness of cells via GPCRs, including GAL1, GAL2, and GAL3 receptors. The study reported that galanin is mainly bound to GAL1 and GAL2 in complex with their primary G protein subtypes Gi and Gq, respectively. Galanin bound to G protein in an α-helical conformation and played an agonistic role, which also indicated that the intracellular loop 2 (ICL2) played an important role in mediating Gq to couple GAL2 receptor by replacing Gi-coupled GAL1R, μOR, 5-HT1AR, and Gs-coupled β2AR and D1R with that of GAL2R. The study shed light on galanin receptor allosteric activation and peptide ligand recognition, and they also identified a general structural component for Gq coupling selectivity. |
| Result |
The results showed two structures of galanin-bound GAL1R-Gi and GAL2R-Gq complexes, which were determined by single-particle cryo-electron microscopy (cryo-EM). Two extensive hydrophobic regions, including ECL2 and a cluster comprising of TM6, ECL3, and TM7, clamp the N-terminal α-helical of galanin with high hydrophobicity onto the extracellular face of both galanin receptors, positing Y9P inserting into a shallow helical pocket. Designing galanin analogs or small molecular chemicals filling the empty region may offer a new therapeutic opportunity for galanin receptor-associated diseases. The article also illustrated the basis of G protein-coupling of galanin receptors and clarified the commonality in the importance of ICL2 on Gq-coupling of GAL2R and other class A GPCRs.
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Fig.2 Role of ICL2 of GAL2R in Gq-coupling selectivity. (Duan, 2022)
References
- Ögren, S. O.; et al. Galanin receptor antagonists. CNS drugs. 2006, 20(8): 633-654.
- Duan, J.; et al. Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors. Nature communications. 2022, 13(1): 1-13.
