PTGDR Membrane Protein Introduction

Introduction of PTGDR

PTGDR is encoded by the PTGDR gene. It belongs to the G-protein-coupled receptor (GPCR) family which provides targets for about 34% of the marketed drugs and account for a global sales volume of over 180 billion US dollars annually. It belongs to prostanoid receptors and cloned based on their high amino acid and cDNA sequence homologies with other GPCRs. PTGDR possess seven transmembrane alpha helices and uses PGD2 as the preferred endogenous ligand, which is a major metabolic product of cyclo-oxygenase (COX)-1 and released after IgE-mediated mast cell activation.

Function of PTGDR Membrane Protein

The activity of PTGDR is mediated by its ligand, prostaglandin D2 (PGD2), which is a major inflammatory mediator produced by mast cells and Th2 cells. PGD2 and its metabolites can be used as selective markers of mast cell activation in vivo. PTGDR is a ubiquitous receptor expressed on various cell types, including inflammatory cells, such as lymphocytes, macrophages, monocytes and basophils and so on. The activation of PTGDR results in the increase of adenylyl cyclase activity, and subsequently enhance the release of cyclic adenosine monophosphate and the activation of protein kinase A. The release of PGD2 from activated mast cells is considered a major allergic and asthma mediators, and development potential and selective PGD2 receptor antagonists might represent useful therapeutic option for allergic and asthma. At the same time, PTGDR is reported to activate the phosphatidylinositol 3-kinase pathway resulting in prevention of apoptosis of human Th2 cells.

Fig.1 Signal transduction mechanisms of activated prostaglandin receptors. (Mohan, 2012)

Application of PTGDR Membrane Protein in Literature

1. Mohan S., et al. Putative Role of Prostaglandin Receptor in Intracerebral Hemorrhage. Frontiers in Neurology. 2012, 3:145. PubMed ID: 23097645
   
   

   This article reviews the current discoveries of prostaglandin receptors and discusses their possible future research directions, resulting in promoting the development of unique therapeutic targets against prostaglandin receptors for the treatment of hemorrhagic stroke and brain injuries alike.

2. Santini G., et al. Investigational prostaglandin D2 receptor antagonists for airway inflammation. Expert Opinion on Investigational Drugs. 2016, 25(6):639-652. PubMed ID: 27094922
   
   

   This article summarizes the pharmacology and the preclinical, phase I and phase II studies of selective PGD2 and PTGDR antagonists.

3. Maher S.A., et al. Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events. Eur. Respir. J. 2015, 45(4):1108. PubMed ID: 25323233
   
   

   Authors in this group apply guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to prove that PGD2 and PTGDR are involved in the symptoms associated with the allergic inflammatory response that characterises asthma and allergic rhinitis.

4. Tippin B.L., et al. Intestinal tumor suppression in Apc(Min/+) mice by prostaglandin D(2) receptor PTGDR. Cancer Medicine. 2014, 3(4):1041-1051. PubMed ID: 24729479
   
   

   This article shows that prostaglandin D2 is a tumor-suppressing molecule because the PTGDR knockouts mice raise median numbers of tumors by 30–40% and the tumor suppression by PGD2 is mediated by its receptor PTGDR.

5. García-Solaesa V., et al. The prostaglandin D2 receptor (PTGDR) gene in asthma and allergic diseases. Allergologia et Immunopathologia. 2014, 42(1):64-68. PubMed ID: 23410912
   
   

   This article evaluates the protective effects of PTGDR in asthma and the functional studies in mice models point out that the expression of PTGDR appears to be associated to the development of asthma or of susceptibility to the disease.

PTGDR Preparation Options

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Reference

1. Mohan S., et al. (2012) Putative Role of Prostaglandin Receptor in Intracerebral Hemorrhage. Frontiers in Neurology. 3:145.

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