Prostanoid GPCR Family Subtypes and Products

What Are Prostanoid Receptors?

Prostanoid receptors are a family of G protein-coupled receptors (GPCRs) comprised of 9 receptor subtypes: DP1, DP2, EP1, EP2, EP3, EP4, FP, IP1, and TP receptors. Prostanoid receptors are involved in a wide variety of functions, and agonist and antagonists have been identified for all 9 receptors. DP receptors play a role in sleep regulation and the allergic response, and DP receptor antagonists have shown potential as an anti-inflammatory. EP receptor antagonists have also shown therapeutic potential as anti-inflammatory agents and antagonist activity has been linked to some involvement in atherothrombotic disease. Prostanoid receptor agonists also have therapeutic applications, as FP agonists are already being used as topical treatments for glaucoma, and IP receptor agonists are being used to treat pulmonary hypertension.

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Prostanoid Receptor Information

Clickable Text Interaction

DP1

DP2

EP1

EP2

EP3

EP4

FP

IP1

TP

The prostaglandin D2 receptor DP1 (DP or PTGDR) is a G protein- coupled receptor for the prostaglandin D2 (PGD2). PGD2 signals through DP2 (CRTH2) to induce TH2, eosinophil, and basophil chemotaxis in a Gαi-dependent manner. In contrast, signaling through DP1 is coupled to Gαs and does not induce chemotaxis.

The chemoattractant-homologous receptor expressed on TH2 cells (CRTH2, also known as DP2 and GPR44) serves as a receptor for prostaglandin D2 (PGD2) and has been reported to mediate PGD2-dependent migration of eosinophils. DP2 mediates the pro-inflammatory effects of PGD2 generated in allergic inflammation. 11-Dehydro- thromboxane B2 (11-dehydro-TXB2) was found to be a full agonist of the DP2 receptor and hence might cause the receptor activation in cellular contexts where PGD-synthase is not present. Antagonism of the 11-dehydro-TXB2/DP2 axis may be of therapeutic relevance.

EP1 receptor (or PTGER1) is a receptor or prostaglandin E2 (PGE2). The receptor may play a role in the smooth muscle contractile response to PGE2 in various tissues. EP1 receptor transactivates EGFR thus activating Akt, while activation of EGFR by its cognate ligand EGF increased COX-2 expression and PGE2 production. This crosstalk between EP1 and EGFR signaling synergistically promotes cancer cell growth and invasion. Some EP1-specific antagonists inhibit osteoclast formation induced by RANKL from the early stage of osteoclastogenesis.

The human prostaglandin E2 (PGE2) receptor EP2 (PTGER2) is abundantly expressed in various tissues including the corneal epithelium of the eye, spinal cord, forebrain, articular cartilage, and kidney. EP2 plays important roles in bronchodilation, dilation of arterioles and venules, blood pressure regulation, smooth muscle relaxation, and bone formation. Modification of PGE2-EP2 receptor signaling may provide a new therapeutic strategy for renal regulation and blood pressure illnesses, as well as bone disease such as osteoarthritis.

Prostaglandin E2 (PGE2) is involved in a number of physiologic and pathophysiologic events in many tissues of the body. The biologic effects of PGE2 are mediated through interaction with specific membrane-bound G protein-coupled prostanoid EP receptors. EP3 receptor (or PTGER3) is expressed as multiple transcripts through alternative splicing, with each transcript showing a different tissue-specific distribution. PGE2 may mediate fever generation in response to both endogenous and exogenous pyrogens by acting at the EP3 receptor. EP3-mediated neuronal pathways converge at corticotropin-releasing hormone containing neurons in the paraventricular nucleus of the hypothalamus to induce HPA axis activation during sickness.

The human prostaglandin E2 (PGE2) receptor EP4 (or PTGER4) is abundantly expressed. Activation of EP4 receptor induces osteoblasts and thereby stimulates de novo bone formation. Results from targeted deletion of the EP4 receptor also suggest that the EP4 subtype of the PGE2 receptor is involved in lipopolysaccharide-induced bone resorption. Modulating EP4 action may thus prove to be clinically useful for the treatment of bacterially induced bone loss, such as in periodontitis and osteomyelitis. EP4 also plays a role in the anti-inflammatory action of PGE2 in human macrophage.

Prostaglandin F (2-alpha) is involved in a number of physiologic processes. It serves as a potent luteolytic agent in many species, has been implicated as a modulator of intraocular pressure, smooth muscle contraction in the uterus and elsewhere. Its effects on cells are mediated through specific interaction with the prostaglandin F receptor (FP or PTGFR). Knockout mice lacking the FP receptor are unable to deliver normal fetuses at term due to a lack of response to oxytocin. The mice also failed to show the decline in serum progesterone expected to precede parturition.

The human prostaglandin I2 receptor IP1 (or PTGIR) mediates the actions of prostaglandin I2 (PGI2 or prostacyclin), which is a labile metabolite of arachidonic acid produced in concert with the bis-enoic prostaglandins via the cyclooxygenase pathway. PGI2 plays a major physiologic role as a strong mediator of vasodilation and inhibitor or platelet activation, and is an antithrombotic agent in vivo and mediates inflammation and pain. PGI2 derived from COX2 plays a critical role in regulating the release of rennin and consequently in renovascular hypertension.

The human TP (thromboxane A2) receptor is a very potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles. It has been shown to be a mediator in diseases such as myocardial infarction, stroke and bronchial asthma. TP receptors can be found on platelets, as well as macrophages, monocytes, vascular endothelial cells, and smooth muscle cells. TP receptor antagonists may also play a role in the treatment of atherothrombosis and stroke prevention.

Prostanoid Cell Lines

Receptor FamilyReceptorSpeciesParentalStable Cell Lines Division-Arrested Cells Membranes
ProstanoidDP1humanHEK293TC1200DC1200MC1200
DP2humanHEK293TH1105DH1105MH1105
DP2humanHEK293TH1105aDH1105aMH1105a
EP1humanHEK293TC1201aDC1201aMC1201a
EP2humanHEK293TC1202DC1202MC1202
EP2mouseHEK293TCm1202DCm1202MCm1202
EP2mouseHEK293TCm1202-3DCm1202-3MCm1202-3
EP2ratHEK293TCr1202DCr1202MCr1202
EP2ratHEK293TCr1202-134DCr1202-134MCr1202-134
EP3humanCHO-K1C1203-1DC1203-1MC1203-1
EP3humanCHO-K1C1203-1aDC1203-1aMC1203-1a
EP3humanCHO-K1C1203-1bDC1203-1bMC1203-1b
EP3humanCHO-K1C1203-1cDC1203-1DCMC1203-1MC
EP3humanCHO-K1C1203-1dDC1203-1dMC1203-1d
EP4humanHEK293TC1204DC1204MC1204
FPhumanHEK293TC1205DC1205MC1205
IP1humanCHO-K1C1206-1DC1206-1MC1206-1
TPhumanHEK293TC1365DC1365MC1365
TPhumanHEK293TH1365H1365H1365

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