Prostaglandin D2 receptor

{{Short description|Mammalian protein found in Homo sapiens}} {{DISPLAYTITLE:Prostaglandin D₂ receptor}}

thumb|Gene expression pattern of the PTGDR gene The '''prostaglandin D₂''' ('''PGD₂''') '''receptors''' are G protein-coupled receptors that bind and are activated by prostaglandin D₂.<ref name="Domingo_2018">{{cite journal | vauthors = Domingo C, Palomares O, Sandham DA, Erpenbeck VJ, Altman P | title = The prostaglandin D₂ receptor 2 pathway in asthma: a key player in airway inflammation | journal = Respiratory Research | volume = 19 | issue = 1 | article-number = 189 | date = September 2018 | pmid = 30268119 | pmc = 6162887 | doi = 10.1186/s12931-018-0893-x | doi-access = free }}</ref><ref name="Brightling_2021">{{cite journal | vauthors = Brightling C, Kulkarni S, Lambrecht BN, Sandham D, Weiss M, Altman P | title = The pharmacology of the prostaglandin D₂ receptor 2 (DP₂) receptor antagonist, fevipiprant | journal = Pulmonary Pharmacology & Therapeutics | volume = 68 | article-number = 102030 | date = June 2021 | pmid = 33826946 | doi = 10.1016/j.pupt.2021.102030 | s2cid = 233184866 }}</ref> Also known as PTGDR or DP receptors, they are important for various functions of the nervous system and inflammation. They include the following proteins:

* Prostaglandin D₂ receptor 1 (DP₁) - {{Gene|PTGDR1}} * Prostaglandin D₂ receptor 2 (DP₂) - {{Gene|PTGDR2}}

== Structure == The PTGDR gene that encodes the prostaglandin D<small>₂</small> receptor in humans is found on the long arm of chromosome 14 at 14q22.1 and consists of four exons.<ref>{{Cite web |title=PTGDR prostaglandin D2 receptor [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/5729#bibliography |access-date=2023-05-13 |website=www.ncbi.nlm.nih.gov}}</ref> A 1995 molecular cloning study of the prostaglandin D2 receptor derived from humans found that the corresponding cDNA encoded for a protein with 359 amino acids and molecular mass of 40,276 daltons.<ref name="Boie_1995">{{cite journal | vauthors = Boie Y, Sawyer N, Slipetz DM, Metters KM, Abramovitz M | title = Molecular cloning and characterization of the human prostanoid DP receptor | journal = The Journal of Biological Chemistry | volume = 270 | issue = 32 | pages = 18910–18916 | date = August 1995 | pmid = 7642548 | doi = 10.1074/jbc.270.32.18910 | doi-access = free }}</ref> The receptor is a heterotrimeric G protein-coupled receptor, containing seven rhodopsin-like transmembrane domains, an extracellular NH2 terminus, and an intracellular COOH terminus.<ref name="Brightling_2021" />

The receptor contains a few structural sites at which it can interact with other molecules. For instance, there are three possible sites for ''N''-glycosylation at the Asn-10, Asn-90, and Asn-297 residues.<ref name="Boie_1995" /> 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.<ref name="Boie_1995" />

== Signal transduction pathway == A 2014 journal article described that the PGD₂ receptor signaling pathway begins with the binding of prostaglandin D<small>₂</small>.<ref name="García-Solaesa_2014" /> After PDG2 binds to the extracellular ligand site on the receptor, the G_s alpha subunit is activated. Activation of the G_s alpha subunit prompts activation of the enzyme adenylate cyclase, which is located on the cell membrane. Adenylate cyclase then catalyzes the change from ATP to cyclic 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.<ref name="García-Solaesa_2014">{{cite journal | vauthors = García-Solaesa V, Sanz-Lozano C, Padrón-Morales J, Hernández-Hernández L, García-Sánchez A, Rivera-Reigada ML, Dávila-González I, Lorente-Toledano F, Isidoro-García M | display-authors = 6 | title = The prostaglandin D2 receptor (PTGDR) gene in asthma and allergic diseases | journal = Allergologia et Immunopathologia | volume = 42 | issue = 1 | pages = 64–68 | date = January 2014 | pmid = 23410912 | doi = 10.1016/j.aller.2012.12.002 | hdl = 10366/158882 | hdl-access = free }}</ref>

However, several other researchers make distinctions between the two prostaglandin D<small>₂</small> receptor subtypes and their G protein-coupled receptor pathways.<ref name="Brightling_2021" /><ref name="Rossitto_2015">{{cite journal | vauthors = Rossitto M, Ujjan S, Poulat F, Boizet-Bonhoure B | title = Multiple roles of the prostaglandin D2 signaling pathway in reproduction | language = en-US | journal = Reproduction | volume = 149 | issue = 1 | pages = R49–R58 | date = January 2015 | pmid = 25269616 | doi = 10.1530/REP-14-0381 | doi-access = free }}</ref> They describe that the binding of PDG₂ to PTGDR1 activates the G_s 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 the G_i alpha subunit, decreasing cAMP levels and increasing intracellular calcium ion levels through inositol phosphate.<ref name="Rossitto_2015" /> These distinctions in signal transduction pathways mediate the different effects of these PDG₂ receptor subtypes.

== Disease relevance == '''Inflammation''': PTGDR1 signaling results in many non-inflammatory effects, such as inhibition of dendritic cell and Langerhans cell migration and eosinophil apoptosis. PTGDR2 mediates several pro-inflammatory effects, including the stimulation of T_H2 cells, ILC2, and eosinophils.<ref name="Domingo_2018" />

'''Asthma''': Activation of PTGDR2 amplifies an inflammation cascade by upregulating the expression and release of type 2 cytokines through T_H2 cells, ILC2 cells, and eosinophils.<ref name="Domingo_2018" /> 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.<ref name="García-Solaesa_2014" />

'''Neurodegeneration''': A 2018 study induced the prostaglandin D₂ signaling pathway in mice via PTGDR2 to determine the impact on Parkinson's Disease-like pathology.<ref>{{cite journal | vauthors = Corwin C, Nikolopoulou A, Pan AL, Nunez-Santos M, Vallabhajosula S, Serrano P, Babich J, Figueiredo-Pereira ME | display-authors = 6 | title = Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets | journal = Journal of Neuroinflammation | volume = 15 | issue = 1 | article-number = 272 | date = September 2018 | pmid = 30236122 | pmc = 6146649 | doi = 10.1186/s12974-018-1305-3 | doi-access = free }}</ref> The researchers observed that the mice with PG treatment developed loss of dopamine neurons in the substantia 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.<ref>George Cotsarelis, Garret Fitzgerald, & Luis Garza, {{US patent|20150072963}} (2015 to University of Pennsylvania Penn).</ref>

== See also == * Eicosanoid receptor * Prostaglandin E₂ receptor

== References == {{Reflist|2}}

== External links == * {{MeshName|Prostaglandin+D2+Receptors}}

{{Transmembrane receptors}} {{G protein-coupled receptors}} {{Prostanoidergics}}

Category:Eicosanoids Category:G protein-coupled receptors