GABAB GPCR Assays
Background of GABAB Receptors
Gamma-Aminobutyric acid (GABA) acts as the primary suppressor of the neurotransmitter, inhibiting the neuronal excitability in the mammalian central nervous system (CNS) as well as modulating the muscle tone. GABAB receptors are metabotropic G protein-coupled receptors, which play a role in suppressing endogenous ligand GABA or other neurotransmitter releases on the presynaptic membrane.
Fig.1 Structure of human GABAB receptor in an inactive state. (Park, 2020)
Distribution and Function of GABAB Receptors
The GABAB receptors are heterodimers of GABAB1 and GABAB2 subunits, located throughout the CNS. The GABAB1 receptor binds to GABA or other ligands, whereas the GABAB2 receptor couples to G proteins. Based on these principles, the clinically targeted drug baclofen for GABAB receptors has been developed. Baclofen, as the GABA derivative and GABAB agonist, has been used for the spastic movement associated with multiple sclerosis and cerebral palsy and addiction to alcohol and drugs to date.
Subtypes and Mechanism of GABAB Receptors
The GABAB receptor family contains two subtypes of receptors, GABAB1 and GABAB2 receptors. The GABAB1 receptor attaches to GABA or other ligands, and the GABAB2 receptor couples to G proteins for the signal transduction.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| GABAB1 receptor | GABBR1 |
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| GABAB2 receptor | GABBR2 |
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Assay List of GABAB Receptor
Creative Biolabs can provide a range of assays of GABAB receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Anti‐inflammatory effects of the GABAB receptor agonist baclofen in allergic contact dermatitis. |
| Journal | Experimental dermatology. |
| Published | 2010 |
| Abstract | The gamma amino butyric acid B (GABAB) is a G protein-coupled receptor (GPCR), which is involved in synaptic transmission. According to recent findings, it is also expressed in immune cells similar to chemokine receptors. Since GPCRs can be heterologously desensitized, the study aimed to investigate the ability of baclofen, a selective agonist of GABAB receptors, to interfere with the function of pro-inflammatory chemokine receptors known to upregulate in skin inflammation. They use both in vitro (human peripheral blood mononuclear cells) and in vivo models (contact hypersensitivity in C57BL/6 mice) to study the agonistic effects of baclofen. |
| Result |
In vitro studies demonstrated that baclofen inhibits CCL2, CCL5, CXCL10, CXCL2, and CX3CL1-induced chemotaxis of human peripheral blood mononuclear cells in a dose-dependent manner. Protein kinase C inhibitors calphostin C and G0 6976 have been shown activated effects on chemotaxis of human peripheral blood mononuclear cells, which had opposite effects to baclofen, indicating that the involvement of both calcium-dependent and -independent protein kinase C in baclofen-induced inhibition of chemokine receptors. In vivo study has indicated that intraperitoneal injection of baclofen significantly mitigated inflammation and recruitment of neutrophils, monocytes, and lymphocytes into the skin. The study demonstrated a new role for the GABAB receptor in inflammation, which might contribute to discovering new therapeutic targets to treat inflammatory skin diseases.
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Fig.2. Gamma amino butyric acid B receptor agonist induces heterologous desensitization of chemokine receptors. (Duthey, 2010)
References
- Park J.; et al. Structure of human GABAB receptor in an inactive state. Nature. 2020, 584: 304-309.
- Duthey, B.; et al. Anti‐inflammatory effects of the GABAB receptor agonist baclofen in allergic contact dermatitis. Experimental dermatology. 2010, 19(7): 661-666.
