Theprostaglandin D2 (PGD2)receptors areG protein-coupled receptors that bind and are activated byprostaglandin D2.[1][2] Also known as PTGDR or DP receptors, they are important for various functions of the nervous system and inflammation. They include the followingproteins:
The PTGDR gene that encodes the prostaglandin D2 receptor in humans is found on the long arm of chromosome 14 at 14q22.1 and consists of four exons.[3] A 1995 molecular cloning study of the prostaglandin D2 receptor derived from humans found that the correspondingcDNA encoded for a protein with 359 amino acids and molecular mass of 40,276 daltons.[4] The receptor is a heterotrimericG protein-coupled receptor, containing seven rhodopsin-like transmembrane domains, an extracellular NH2 terminus, and an intracellular COOH terminus.[2]
The receptor contains a few structural sites at which it can interact with other molecules. For instance, there are three possible sites forN-glycosylation at the Asn-10, Asn-90, and Asn-297 residues.[4]Protein kinase C can also phosphorylate the prostaglandin D2 receptor at two sites in the first and second cytoplasmic loops as well as at six sites in the COOH terminus.[4]
A 2014 journal article described that the PGD2 receptor signaling pathway begins with the binding of prostaglandin D2.[5] After PDG2 binds to the extracellular ligand site on the receptor, the Gs alpha subunit is activated. Activation of the Gs alpha subunit prompts activation of the enzymeadenylate cyclase, which is located on the cell membrane. Adenylate cyclase then catalyzes the change from ATP tocyclic AMP, or cAMP. The result of the PDG2 receptor signaling pathway is a rise in levels of second messenger cAMP, which can proceed to perform other tasks depending on the activated cell.[5]
However, several other researchers make distinctions between the two prostaglandin D2 receptor subtypes and their G protein-coupled receptor pathways.[2][6] They describe that the binding of PDG2 to PTGDR1 activates theGs alpha subunit, resulting in the subsequent increase of cAMP. This stimulation of cAMP also involves activation of Protein Kinase A and influx of calcium ions through membrane channels. In contrast, the binding of PDG2 to PTGDR2 instead activates theGi alpha subunit, decreasing cAMP levels and increasing intracellular calcium ion levels through inositol phosphate.[6] These distinctions in signal transduction pathways mediate the different effects of these PDG2 receptor subtypes.
Inflammation: PTGDR1 signaling results in many non-inflammatory effects, such as inhibition ofdendritic cell andLangerhans cell migration andeosinophil apoptosis. PTGDR2 mediates several pro-inflammatory effects, including the stimulation ofTH2 cells,ILC2, and eosinophils.[1]
Asthma: Activation of PTGDR2 amplifies an inflammation cascade by upregulating the expression and release oftype 2 cytokines through TH2 cells, ILC2 cells, and eosinophils.[1] These type 2 cytokines lead to symptoms like airway inflammation, increased mucus production, and mucus metaplasia, which are found in asthma conditions. Increase in PTGDR1 signal transduction results in vasodilation, which can promote the migration and likelihood of survival for inflammatory cell types.[5]
Neurodegeneration: A 2018 study induced the prostaglandin D2 signaling pathway in mice via PTGDR2 to determine the impact onParkinson's Disease-like pathology.[7] The researchers observed that the mice with PG treatment developed loss of dopamine neurons in thesubstantia nigra pars compacta, motor deficits, and other progressive disease-like symptoms. They also discovered PGD2 receptors on dopaminergic cells but not on microglia.
Hair growth: The invention relates to compositions and methods for regulating hair growth. Specifically, the invention relates to regulating hair growth by regulating the activity one of the prostaglandin D2 (PGD2) receptors, DP-2 (GPR44). Compositions and methods for regulating hair growth include inhibiting hair growth by administering a DP-2 agonist, or stimulating hair growth by administering a DP-2 antagonist.[8]