GPR18 - G-Protein Coupled Receptor 18 | Elisa - Clia - Antibody - Protein

Background:

GPR18 is a G protein-coupled receptor that belongs to the class A (rhodopsin-like) family of GPCRs. GPR18 was identified in the early 2000s through bioinformatics and molecular cloning techniques. GPR18 is expressed in various tissues and organs, including the brain, immune cells, gastrointestinal tract, and peripheral tissues. GPR18 has been implicated in mediating the effects of various endogenous and exogenous ligands, including N-arachidonoyl glycine (NAGly) and abnormal cannabidiol (Abn-CBD). GPR18 has a diverse expression patterns and potential roles in immune modulation, inflammation, and neurological function. While its exact physiological functions and signaling mechanisms are still being elucidated, GPR18 represents a promising target for therapeutic intervention in a range of diseases.

Structure:

Extracellular N-Terminus:

The N-terminal domain of GPR18 is extracellular and relatively short. It plays a role in ligand recognition and binding.

Transmembrane Domain (TMD):

• The TMD consists of seven transmembrane alpha-helices (TM1 to TM7). These helices are arranged in a characteristic bundle that spans the cell membrane.
• Helices Arrangement: The seven transmembrane helices create a helical bundle that forms a binding pocket within the membrane plane. This pocket is essential for ligand binding and receptor activation.
• Ligand Binding Pocket: The ligand binding pocket is located within the transmembrane region, involving residues from several helices. Specific helices such as TM3, TM5, TM6, and TM7 play crucial roles in ligand interaction.

Extracellular Loops (ELs):

The three extracellular loops (EL1, EL2, EL3) connect the transmembrane helices on the extracellular side. These loops contribute to ligand binding and receptor stability. EL2 is particularly important for forming the binding site and maintaining receptor conformation.

Intracellular Loops (ILs):

The three intracellular loops (IL1, IL2, IL3) connect the transmembrane helices on the intracellular side. These loops are critical for G protein coupling and signal transduction. IL3 and the C-terminal tail are especially important for interacting with G proteins and other intracellular signaling molecules.

Intracellular C-Terminus:

The C-terminal tail of GPR18 is located intracellularly and is involved in signal transduction and interaction with intracellular proteins. It may contain sites for phosphorylation, which can regulate receptor activity and desensitization.

 Physiological Functions:

• Endocannabinoid System: GPR18 has been proposed as a putative receptor for certain endocannabinoids, although its exact role within the endocannabinoid system is still under investigation.
• Immune Modulation: GPR18 activation has been shown to modulate immune responses, including cytokine production and leukocyte migration, suggesting a potential role in inflammation and immune regulation.
• Neurological Functions: GPR18 is expressed in the brain and has been implicated in the regulation of neuronal signaling and neurotransmitter release, although its specific functions in the central nervous system are not fully understood.

Clinical Implications:

• Inflammation and Immune Disorders: GPR18 may represent a novel target for the development of anti-inflammatory and immunomodulatory therapies for conditions such as inflammatory bowel disease (IBD), rheumatoid arthritis, and multiple sclerosis.
• Neurological Disorders: GPR18 dysregulation has been implicated in neurological disorders such as epilepsy, neuropathic pain, and neuroinflammation, suggesting potential therapeutic implications.

Therapeutic Potential:

• Drug Development: GPR18 agonists and antagonists are being investigated for their therapeutic potential in various diseases, including inflammation, immune disorders, and neurological conditions.
• Precision Medicine: Targeting GPR18 signaling pathways may offer personalized treatment strategies for individuals with conditions associated with dysregulated immune responses or neuronal dysfunction.